#3. Like tears in rain, we are replicants

Forever young?
Mar 12, 2018 · 8 min read

Replicants are the unsettling human-like clones in the Blade Runner movies. They are programmed to die — most of them in just four years — so they have the consciousness and intelligence of normal humans combined with the knowledge that they have just a few blinks of an eye to live.

Like tears in rain, to use the memorable line from Rutger Hauer’s character in the first (1982) Blade Runner movie, replicants are destined to leave barely a mark on the universe they so briefly inhabit.

New research is revealing that we real humans aren’t that different, however, because we too are programmed to die. We are programmed to die in about eighty years — twenty or so times the allotted timespan of replicants, but still just a few blinks of an eye.

Programmed? Yes. Here’s how.

Josh Mitteldorf and Dorian Sagan’s excellent 2016 popular science book, Cracking the Aging Code, describes the current biological theories of aging, knocking down the usual contenders one by one and leaving only Mitteldorf’s theory standing. His theory, known as the Demographic Theory of Aging, makes the case that we and other mammals could live much longer if our bodies didn’t go into programmed self-destruct mode.

They argue that most of the symptoms of aging that we all accept as natural and generally inevitable are actually programmed into our bodies by evolution. They’re not inevitable. Aging is not inevitable. Many animal and plant species don’t age, so there is nothing universal or necessarily “natural” about aging.

Why would evolution program our deaths?

The short answer is that nature seems to have found a way to enhance the survival of species and entire ecosystems in a way that requires that individual organisms die long before their maximum lifespan is up. There are a few animal species that don’t age, such as lobsters, hydras, some jellyfish, and perhaps naked mole rats, and surely more that we’ll discover in the coming years. And there are a great many plant species that don’t age; trees, for example, generally keep growing until they fall over from their own weight, landslides, or get hit by lightning.

All organisms still die at some point, however, of various causes, as far as we know. But the fact that many species don’t actually age highlights the possibility that it isn’t always “natural” to age and die from old age.

Mitteldorf’s argument is that natural selection works at all levels (genetic, organismic, species, ecosystem, and perhaps other levels), not just on individuals, and this multi-level selection process finds a balance between the various levels of selection by inventing aging and early death in each organism.

Each organism, by aging and dying, ensures that variation continues to arise in the population with the introduction of new genes, through mutation, sex, and epigenetic variations, from generation to generation. If organisms don’t age, populations are more vulnerable to booms and busts, and therefore extinctions. Such populations are also less able to adapt to changing environments because organisms that don’t die, even if they produce new gene variants in their offspring, don’t have the genetic toolbox that arises in steadily aging, dying, and reproducing organisms.

By aging and dying, each organism makes way, eventually, for the next generation — and all the new genetic variations that the new generation brings. If organisms stayed around forever and became stronger and stronger, there would be little room for more diverse offspring to make their way in the world.

What this adds up to is that despite a loss of genetic fitness for an individual suffering from a programmed death — think of the salmon swimming upstream to spawn and then dying immediately after and thus forgoing any future spawning events — the species as a whole, and its gene pool, does better because it is able to generate far more genetic variations, through the generational turnover of individuals, and thus make it through the lean times that always arise at various times in any environment.

Species that don’t have organismic aging are far less able to weather such lean times, and will generally die off and make way for similar species that do include aging and death of individuals. So natural selection promotes aging as a solution to a broad set of survival problems. The end result is that the large majority of animals do indeed age and die from old age.

These ideas require reconsideration of some aspects of the widely accepted neo-Darwinian evolutionary perspective. Cracking the Aging Code goes through all of the standard objections in a pretty convincing manner. Debate will surely continue on the details, but I was convinced of the general plausibility of the theory.

Mitteldorf’s ideas are not yet widely accepted but it is becoming more widely accepted that at least some aspects of animal aging are programmed by our own genes.

For example, it is now well-known that most of our cells have about 50 cell divisions available before their telomeres shrink down and the chromosomes fall apart, preventing any more cell divisions, and eventual cell death. In this way, and others, it seems that cell aging and death is indeed pre-programmed.

Why would evolution have arrived at this type of programmed cell death? It is thought that limited cell division is a solution for preventing or mitigating cancer. If cells generally can’t reproduce more than 50 times, might this prevent many cancers?

Mitteldorf argues, however, that this cancer-based theory doesn’t make sense because obviously cancer is still quite common in humans. And germ line cells (sperm and eggs) don’t suffer from steadily shortening telomeres at all. Mitteldorf argues instead that telomere shortening is one of many ways that our bodies are programmed to die because of all the reasons just discussed.

We are, then, longer-lived replicants. But we’re still programmed to die. And as these truths become more widely known we’ll surely see more and more people clamoring to change what natural selection has wrought.

We are now fast entering an era in which artificial selection is taking over from natural selection and we will soon become masters of our own fate instead of victims of blind natural selection. We can already select the gender of our children with simple genetic engineering (centrifuging sperm, for example). We are also now beginning to see designer gene therapies for treating cancer, but also for more aesthetic or commercial purposes.

Jennifer Doudna’s 2017 book, A Crack in Creation, is all about the CRISPR gene editing revolution, which allows editing single base-pairs of DNA with precision. We can at this point, change any gene we want to in ourselves or other species. This is empowering and frightening at the same time.

We are just at the beginning of this major new trend but major progress in curing illness with these new types of therapies is already occurring. In the last six months, the FDA approved three new gene therapy cancer treatments that, while very expensive (some as much as half a million dollars for a single treatment), promise to be extremely effective, with a cure for most patients likely with only a single treatment. These new treatments are also likely to be the leading edge of a large wave of new gene therapy cancer treatments.

Solving cancer is only one of many issues we’ll need to solve if we are to solve aging itself. A 2013 paper describes ten “hallmarks of aging”: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication.

Cancer is a type of genomic instability and any human that lives long enough will get cancer eventually. So solving cancer is a key part of the puzzle, yet far from the only part. It will probably take many years for scientists to figure out how to solve all of these ten hallmarks of aging — but it is now plausible to seriously consider this possibility.

Mitteldorf’s theory of aging helps to explain why we age and also suggests some strategies for solving aging that may not make sense within the traditional theories of aging.

For example, there is good evidence in many species that caloric restriction — eating less calories — leads to significantly longer lifespans. This didn’t seem to make much sense under traditional theories of aging. Why would less food and increased bodily stress from less food lead to longer lives? Well, under Mitteldorf’s approach it makes good sense: basically, organisms are programmed to die earlier than would otherwise be the case when there is plenty of food and a relative lack of stress, to make way for the next generation and promote population health.

It is only when stress (hormesis, to use the biological term) is present that preprogrammed dying activities relax a bit. It’s counterintuitive, but there is good evidence for both the fact of longer lives from hormesis, as well as Mitteldorf’s explanation for this phenomenon.

It’s been understood for some time that reducing caloric intake can lead to longer lives. We are now learning, in the last few years, however, that various types of “intermittent fasting” can simulate the effects of caloric restriction in a way that our general quality of life doesn’t have to suffer, while retaining the benefits of caloric restriction in terms of better health and long lifespans. Fasting even one day a week may induce the desired effect. Or only eating during a limited window each day, for example, a six-hour timespan each day, and thus achieving an 18-hour fast each day, may also produce beneficial effects.

Similarly, exercise is a type of body stress that leads to hard-to-exaggerate health improvements. While it may also be counter-intuitive that stressing your body out with vigorous exercise — “wearing it out” — would actually lead to longer lifespans and healthspans, there is also abundant evidence that regular vigorous exercise can result in substantial beneficial effects.

One area where it seems hormesis is not a good idea is sleep. We should all target 7–8 hours of good sleep each night since the effects of not achieving sufficient sleep have been shown in recent years to have remarkably negative impacts on performance of all types. (See Matthew Walker’s new book Why We Sleep for more on this.)

For me, reading Cracking the Aging Code was a series of mind-blowing moments because it had not occurred to me before — and I suspect it had not occurred to you — that evolution may have literally programmed our early death. Our bodies are killing themselves/us before our very eyes.

This series of revelations occurred with me because we are taught from an early age, during the course of our modern education, that natural selection works on individuals and genes only, and that “group selection” is a forbidden term. Mitteldorf and Sagan tackled that sacred cow in a convincing way as they argue for their multi-level selection approach instead of the traditional individual-only approach to selection.

Once we accept that it makes sense in some circumstances that nature could evolve early death programs, we start to see our own lives and our potential for longer and happier lives in a whole new light.

If we are indeed long-lived replicants, we’re also very smart replicants who are on the verge of figuring out how to undo the eons-old programming built into our genetic code. I look forward to the new choices that will be made available with this major shift in humanity’s potential.

Tam Hunt is a lawyer and a writer.