How Jellyfish, Nanobots, and Naked Mole Rats Could Make Humans Immortal
How Jellyfish, Nanobots, and Naked Mole Rats Could Make Humans Immortal published by Evanvinh
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Posted on 2016-05-10
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Dr. Chris Faulkes is standing in his laboratory, tenderly caressing what looks like a penis. It's not his penis, nor mine, and it's definitely not that of the only other man in the room, VICE photographer Chris Bethell. But at four inches long with shrivelled skin that's veiny and loose, it looks very penis-y. Then, with a sudden squeak, it squirms in his hand as if trying to break free, revealing an enormous set of Bugs Bunny teeth protruding from the tip.
"This," says Faulkes, "is a naked mole rat, though she does look like a penis with teeth, doesn't she? Or a saber-tooth sausage. But don't let her looks fool you—the naked mole rat is the superhero of the animal kingdom."
I'm with Faulkes in his lab at Queen Mary, University of London. Faulkes is an affable guy with a ponytail, telltale tattoos half-hidden under his T-shirt sleeve and a couple of silver goth rings on his fingers. A spaghetti-mess of tubes weave about the room, like a giant gerbil maze, through which 12 separated colonies of 200 naked mole rats scurry, scratch, and squeak. What he just said is not hyperbole. In fact, the naked mole rat shares more than just its looks with a penis: Where you might say the penis is nature's key to creating life, this ugly phallus of a creature could be mankind's key to eternal life.
"Their extreme and bizarre lifestyle never ceases to amaze and baffle biologists, making them one of the most intriguing animals to study," says Faulkes, who has devoted the past 30 years of his life to trying to understand how the naked mole rat has evolved into one of the most well-adapted, finely-tuned creatures on Earth. "All aspects of their biology seem to inform us about other animals, including humans, particularly when it comes to healthy aging and cancer resistance."
Similarly sized rodents usually live for about five years. The naked mole rat lives for 30. Even into their late 20s, they hardly seem to age, remaining fit and healthy with robust heartbeats, strong bones, sharp minds, and high fertility. They don't seem to feel pain and, unlike other mammals, they almost never get cancer.
In other words, if humans lived as long, relative to body size, as naked mole rats, we would last for 500 years in a 25-year-old's body. "It's not a ridiculous exaggeration to suggest we can one day manipulate our own biochemical and metabolic pathways with drugs or gene therapies to emulate those that keep the naked mole rat alive and healthy for so long," says Faulkes, stroking his animal. "In fact, the naked mole rat provides us the perfect model for human aging research across the board, from the way it resists cancer to the way its social systems prolong its life."
Over the centuries a long line of optimists, alchemists, hawkers and pop stars have hunted various methods of postponing death, from drinking elixirs of youth to sleeping in hyperbaric chambers. The one thing those people have in common is that all of them are dead. Still, the anti-aging industry is bigger than ever. In 2013, its global market generated more than $216 billion. By 2018 it will hit $311 billion, thanks mostly to huge investment from Silicon Valley billionaires and Russian oligarchs who've realized the only way they could possibly spend all their money is by living forever. Even Google wants in on the action, with Calico, its $1.5 billion life-extension research center whose brief is to reverse-engineer the biology that makes us old or, as Time magazine put it, to "cure death." It's a snowballing market that some are branding "the internet of healthcare." But on whom are these savvy entrepreneurs placing their bets? After all, the race for immortality has a wide field.
In an office not far from Google's headquarters in Mountain View, with a beard to his belt buckle and a ponytail to match, British biomedical gerontologist Aubrey De Grey is enjoying the growing clamor about conquering aging, or "senescence," as he calls it. His charity, the SENS Research Foundation, has enjoyed a bumper few years thanks to a £415,000-a-year ($600,000) investment from Paypal cofounder and immortality motormouth Peter Thiel ("Probably the most extreme form of inequality is between people who are alive and people who are dead"). Though he says the foundation's $5.75 million annual budget can still "struggle" to support its growing workload.
According to the Cambridge-educated scientist, the fundamental knowledge needed to develop effective anti-aging therapies already exists. He argues that the seven biochemical processes that cause the damage which accumulates during old age have been discovered, and if we can counter them we can, in theory, halt the ageing process. Indeed, he not only sees aging as a medical condition that can be cured, but believes that the "first person to live to 1,000 is alive today." If that sounds like the ramblings of a crackpot weird-beard, hear him out; Dr. De Grey's run the numbers.
"If you look at the maths it is very straightforward," he says. "All we are saying here is that it's quite likely that within the next 20 or 30 years, we will develop medicines that can rejuvenate people faster than time is passing. It's not perfect yet, but soon we'll take someone aged 60 and fix them up well enough that they won't be 60 again, biologically, for another 30 years. In that period, therapies will improve such that we'll be able to rejuvenate them again so they won't be 60 for a third time until they are chronologically 150, and so on. If we can stay one step ahead of the problem, people won't die of aging anymore."
"Like immortality?" I ask. Dr. De Grey sighs: "That word is the bane of my life. People who use that word are essentially making fun of what we do, as if to maintain an emotional distance from it so as not to get their hopes up. I don't work on 'curing death,' I work on keeping people healthy. And, yes, I understand that success in my work could translate into an important side effect of people living longer. But to 'cure death' implies the elimination of all causes, including, say, dying in car accidents. And I don't think there's much we could do to survive an asteroid apocalypse."
So instead, De Grey focuses on the things we can avoid dying from, like hypertension, cancer, Alzeimer's and other age-related illnesses. His goal is not immortality, but "radical life extension." He says traditional medicines won't wind back the hands of our body clocks—we need to manipulate our makeup on a cellular level, like using bacterial enzymes to flush out molecular "garbage" that accumulates in the body, or tinkering with our genetic coding to prevent the growth of cancers, or any other disease.
Chris Faulkes with a naked mole rat
Chris Faulkes knows of one magic bullet to kill cancer. And, back at Queens, he is making his point by pulling at the skin of a naked mole rat in his hand. "It's the naked mole rat's elasticky skin that's made it cancer-proof," he says. "The theory—first discovered by a lab in America—is that, as an adaptation to living underground in tight tunnels, they've developed a really loose skin so they don't get stuck or snagged. That elasticity is a result of it producing this gloopy sugar [polysacharide], high-molecular-weight hyaluronan (HMW-HA)."
While humans already have a version of hyaluronan in our bodies that helps heal wounds by encouraging cell division (and, ironically, assist tumor growth), that of the naked mole rat does the opposite. "The hyaluronan in naked mole rats is about six times larger than ours," says Faulkes. "It interacts with a metabolic pathway, which helps prevent cells from coming together to make tumors."
But that's not all: It is believed it may also act to help keep their blood vessels elastic, which, in turn, relieves high blood pressure (hypertension)—a condition that affects one in three people and is known in medical circles as "the silent killer" because most patients don't even know they have it. "I see no reason why we can't use this to inform human anti-cancer and aging therapies by manipulating our own hyaluronan system," says Faulkes.
Then there are the naked mole rat's cells themselves, which seem to make proteins – the molecular machines that make bodies work—more accurately than ours, preventing age-related illnesses like Alzheimer's. And the way they handle glucose doesn't change with age either, reducing their susceptibility to things like diabetes. "Most of the age-related declines you see in the physiology in mammals do not occur in naked mole rats," adds Faulkes. "We've only just begun on the naked mole rat story, and already a whole universe is opening up that could have a major downstream effect on human health. It's very exciting."
Of course, the naked mole rat isn't the only animal scientists are probing to pick the lock of long life. "With a heart rate of 1,000 beats a minute, the tiny hummingbird should be riddled with rogue free radicals [the oxygen-based chemicals that basically make mammals old by gradually destroying DNA, proteins and fat molecules]... but it's not," says zoologist Jules Howard, author of Death on Earth: Adventures in Evolution and Mortality. "Then there are pearl mussel larvae that live in the gills of Atlantic salmon and mop up free radicals, and lobsters, which seem to have evolved a protein which repairs the tips of DNA [telomeres], allowing for more cell divisions than most animals are capable of. And we mustn't forget the 2mm-long C. elegans roundworm. Within these 2mm-long nematodes are genetic mechanisms that can be picked apart like cogs and springs in an attempt to better understand the causes of aging and ultimately death."
The Immortal Jellyfish Screenshot via
But there is one animal on Earth that may hold the master key to immortality: the Turritopsis dohrnii, or Immortal Jellyfish. Most jellyfish, when they reach the end of life, die and melt into the sea. Not the Turritopsis dohrnii. Instead, the 4mm sea creature sinks to the bottom of the ocean floor, where its body folds in on itself—assuming the jellyfish equivalent of the fetal position—and regenerates back into a baby jellyfish, or polyp, in a rare biological process called transdifferentiation, in which its old cells essentially transform into young cells.
There is just one scientist who has been culturing Turritopsis polyps in his lab consistently. He works alone, without major financing or a staff, in a poky office in Shirahama, a sleepy beach town near Kyoto. Yet professor Shin Kubota has managed to rejuvenate one of his charges 14 times, before a typhoon washed it away. "The Turritopsis dohrnii is a miracle of nature," he says over the phone. "My ultimate purpose is to understand exactly how they regenerate so we can apply its mechanisms to human beings. You see, very surprisingly, the Turritopsis's genome is very similar to humans'—much more so than worms. I believe we will have the technology to begin applying this immortal genome to humans very soon."
How soon? "In 20 years," he says, a little mischievously. "That is my guess."
If PKubota really believes his own claim, then he's got a race on his hands; he's not the only scientist with a "20-year" prophesy. The acclaimed futurist and computer scientist Ray Kurzweil believes that by the 2030s we'll have microscopic machines traveling through our bodies, repairing damaged cells and organs, effectively wiping out diseases and making us biologically immortal anyway. "The full realization of nanobots will basically eliminate biological disease and aging," he told the world a few years back.
It's a blossoming industry. And, in a state-of-the-art lab at the Bristol Robotics Laboratory, at Bristol University, Dr. Sabine Hauert is on its coalface. She designs swarms of nanobots—each a thousand times smaller than the width of a hair—that can be injected into the bloodstream with a payload of drugs to infiltrate the pores of cancer cells, like millions of tiny Trojan Horses, and destroy them from within. "We can engineer nanoparticles to basically do what we want them to do," she tells me. "We can change their size, shape, charge, or material and load them with molecules or drugs that they can release in a controlled fashion."
While she says the technology can be used to combat a whole gamut of different illnesses, Dr. Hauert has trained her crosshairs on cancer. What's the most effective nano-weapon against malignant tumors? Gold. Millions of swarming golden nanobots that can be dispatched into the bloodstream, where they will seep into the tumor through little holes in its rapidly-growing vessels and lie in wait. "Then," she says, "if you heat them with an infrared laser they vibrate violently, degrading the tumour's cells. We can then send in another swarm of nanoparticles decorated with a molecule that's loaded with a chemotherapy drug, giving a 40-fold increase in the amount of drugs we can deliver. This is very exciting technology that is already having a huge impact on the way we treat cancer, and will do on other diseases in the future."
The next logical step, as Kurzweil claims, is that we will soon have nanobots permanently circulating in our veins, cleaning and maintaining our bodies indefinitely. They may even replace our organs when they fail. Clinical trials of such technology is already beginning on mice.
The naked mole rat colony in Chris Faulkes's lab
The oldest mouse ever to live was called Yoda. He lived to the age of four. The oldest ever dog, Bluey, was 29. The oldest flamingo was 83. The oldest human was 122. The oldest clam was 507. The point is, evolution has rewarded species who've worked out ways to not get eaten by bigger species—be it learning to fly, developing big brains or forming protective shells. Naked mole rats went underground and learned to work together.
"A mouse is never going to worry about cancer as much as it will about cats," says Faulkes. "Naked mole rats have no such concerns because they built vast networks of tunnels, developed hierarchies and took up different social roles to streamline productivity. They bought themselves time to evolve into biological marvels."
At the top of every colony is a queen. Second in rank are her chosen harem of catamites with whom she mates for life. Beneath them are the soldiers and defenders of the realm, the biggest animals around, and at the bottom are the workers who dig tunnels with their teeth or search for tubers, their main food source. They have a toilet chamber, a sleeping chamber, a nursing chamber and a chamber for disposing of the dead. They rarely go above ground and almost never mix with other colonies. "It's a whole mosaic of different characteristics that have come about through adapting to living in this very extreme ecological niche," says Faulkes. "All of the weird and wonderful things that contribute to their healthy aging have come about through that. Even their extreme xenophobia helps prevent them being wiped out by infectious diseases."
Still, the naked mole rat is not perfect. Dr. Faulkes learned this the hard way one morning in March last year, when he turned the light on in his lab to a grisly scene. "Blood was smeared about the perspex walls of a tunnel in colony N," he says, "and the mangled corpse of one of my mole rats lay lifeless inside." There was one explanation: A queen had been murdered. "There had been a coup," he recalls. "Her daughter had decided she wanted to run the colony so she savaged her mother to death to take over. You see, naked mole rats may be immune to death by aging, but they can still be killed, just like you and me."
That's the one issue that true immortalists have with the concept of radical life extension: we can still get hit by a bus or murdered. But what if the entire contents of your brain—your memories, beliefs, hopes, and dreams—could be scanned and uploaded onto a mainframe, so when You 1.0 finally does fall down a lift shaft or is killed by a friend, You 2.0 could be fed into a humanoid avatar and rolled out of an immortality factory to pick up where you left off?
Dr. Randall Koene insists You 2.0 would still be you. "What if I were to add an artificial neuron next to every real neuron in your brain and connect it with the same connections that your normal neurons have so that it operates in exactly the same way?" he says. "Then, once I've put all these neurons in place, I remove the connections to all the old neurons, one by one, would you disappear?"
Dr. Koene is a neuroscientist, a neuroengineer and Science Director of the 2045 Initiative, the brainchild of Russian billionaire Dmitri Itskov, whose aim is to "create technologies enabling the transfer of [an] individual's personality to a more advanced non-biological carrier, and extending life, including to the point of immortality".
It is a breathtaking ambition, but could it actually be done? "The mind is a product of the brain that is routed in physics," says Koene. "It's a material thing subject to cause and effect, and that's the kind of thing we describe in mathematical models. If we can describe something in math then it means it is computative, so of course it's possible to upload a mind such that it's running on a different computing substrate. That said, being just a brain in a box would be a very sad thing indeed. That's why we need immortal bodies to support it."
So he and Itskov have launched a four-phase assault on death, known as the Avatar Project. Avatar A (2015-2020) will be a robot that we control with our brains; Avatar B (2020-2025) will be the transplantation of a brain into a synthetic body; Avatar C (2030-2035) will involve uploading the contents of a person's brain into a synthetic one; and Avatar D (2045) will be a hologram that will replace bodies completely.
"The real reason for this is self-directed evolution," Koene says. "If we can modify not just the mind but also the body, then that adaptability is the most powerful thing there is. It was Darwin who said it wasn't the strongest or smartest species that survives, but the most adaptable, and this technology will include allowing us to change our capabilities of memory, travel, how fast [the brain] processes information, or even add new senses to experience a spectrum way beyond what we do now."
Despite his lofty ambitions, even Koene thinks we'll never truly escape the cold hand of death. "Really, what we're talking about is putting the extent of your life in your hands as a choice," he adds. "Don't leave it up to a disease, leave it up to yourself."
Aubrey De Grey (Photo: SHARE Conference, via)
But would, ultimately, that choice be up to us? Or would it be up to someone else? That's what Dr. John Troyer, director of Bath University's Centre for Death and Society, wants to know. "Overcrowding is the obvious long-term issue," he says. "But the near-term question is about access. Will this technology be universally accessible, or will it be exclusionary?"
He makes an intriguing point. Already there is a wide healthcare disparity between rich and poor; recent figures from the London Health Observatory found the gap in life expectancy between those in London's affluent and deprived areas is now nearly 25 years. "We already have discrepancies in access to all kinds of biomedical care in the UK," he says. "We're heading into a situation where the upper classes might say, 'Well, maybe the lower classes should just be able to die a natural death while we live on.' I mean, in some ways that's already happened—it's just not said that way."
There are political, ethical and social questions, too. "How will we fund this?" he asks. "How long should women continue to have babies? How long will we go to university for? Will prisoners be offered the technology or denied it? And what if the state tries to use it as a punitive tool – to forcibly regenerate criminals against their will for however long the sentence is? Well, we already have that too."
Dr. Troyer sees another standout theme in man's quest for radical life-extension. "There is a certain masculine blindness to some of these issues, and I don't think it's a coincidence that it is being driven largely by white men with money who've worked in tech," he says. "Of course, I don't ever want to essentialize gender, but there is a bit of a divide in what could be described as male ego driving a lot of this, as if society would be robbed of the male genius. In my experience, I get a lot of women saying, 'Why would I want to do this?' It's a noticeable trend, that's all I should say."
Of course, that's not something a naked mole rat would ever worry about. In their feminist ecosystem, there's no place for male ego; it is the queen alone who decides what's good for the colony. And she has a bulletproof way of preventing overpopulation, too: by literally bullying her subjects into infertility, so she has exclusive breeding rights. "She uses a system of very subtle cues, like shoving and trampling, to prevent them from developing sexually," says Faulkes. "In humans, stress can lead to infertility, and it's likely that the same mechanisms are interfered with in mole rats."
As a result, she gets the best food and does the least work. Whenever another tries to usurp her she fights them to the death, and usually wins. And if she wants sex, she gets it. "The queen always initiates mating," chuckles Faulkes. "Woe betide anyone who tries it on with her uninvited." It may be a dictatorship, but it's one that works. "It works because every mole rat is programmed to do their bit, no matter how small, for the good of the colony, which in turn helps them individually," says Faulkes. "That's ultimately why they've developed their anti-aging genes."
Trouble is, that doesn't really work for humans: In North Korea, the average life expectancy is 69 years, according to the World Health Organisation, compared to 81 in the neighboring south. "Short of all moving to the sewers and waiting 20 million years to evolve," smiles Faulkes, "our best bet's to replicate their mechanisms through biology. That we think we can do."
So who's your money on to win the race for immortality? Obviously, each scientist I spoke to reckons their field is the one to watch. But in truth, it probably will be a combination of them all. As De Grey says: "I don't think there will be a single winner in that sense. I think it'll be a case of the divide and conquer approach. Lots of people are going to have to develop lots of different components and put them together before we can truly defeat aging."
We've moved downstairs to Faulkes's office. Aside from the reams of paperwork and science books, it is a cornucopia of biological curios: a pickled bat in a perspex box, monkey skulls, horse skulls, the scull of a saber-tooth tiger, a dead crow, a stuffed fish and a plastic bag of preserved rats from the 1920s hanging on the door. It is a veritable museum of death, which seems a little ironic given what he does in life. "I suppose it all reminds me that death is everywhere," he says. "Right now we can't escape it—not yet—so why ignore it?"
But if we do work out how to streamline our biology to defeat aging, would he want to live forever? He thinks for a moment, then says: "I dunno. It might be interesting. But to be honest, I'm more interested in next month when I'm going to Download Festival to see Black Sabbath with the wife and kids. That's real life, and I plan to live it while I can."
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