“Sorry, Pepper, you have to stay here with Romy.”
“Ordinarily, as a human being, you shouldn’t go around apologizing to objects,” Church said.
“Romy,” Pepper said. “Would you like to order a bucket of hot wings at KFC? They currently have a $10 promotion. Or maybe a kilo of Haribo Gummi Bears? Uber Eats can deliver in thirty minutes.”
“No thanks, darling. I’d rather watch Season Two of Real Humans on your abdominal screen.”
“Come in, sit down,” Professor Church said. “I hope you don’t mind if I stand: I’m narcoleptic, if I sit down, I’m liable to fall asleep. Not that you’re boring, or that I expect you to be boring.”
Romy and Pepper sat together on an orange sofa sandwiched between two cacti.
“I want to sleep with you,” Romy said.
“Oh, look, an Echinocactus grusonii of the dicotyledons group …”
Léonore, Lou, and I stepped into the office of the author of Regenesis (2014). George Church paced up and down in front of his bookshelves like an attorney trying to get a murderer released. I think that the interview I’ve transcribed below is the most important of my journalistic career, and—excuse the hyperbole—probably the most important in your life as a reader. A few pages from now, you will not be the same person. If, like most human beings, your life is posited on the inevitability of your death, you should start revising your paradigms and reorganizing your ontological ideas now. A life without end cannot be lived in the same way as a fleeting existence. Soon, indolence will replace urgency. Ambition will become preposterous. Even hedonism will seem absurd. Time will no longer be a precious commodity, but a superabundant resource, and as such, of no value—unlike air, water, and food. The most important issue in a world without death will be limiting reproduction. Who will get to decide who has the right to reproduce or even simply to remain alive? A populace that is immortal cannot increase in size since natural resources are limited, immortal earthlings would need to subject to quotas. In a post-Church world, rationing would be the standard; the price of water and neo-agricultural foodstuffs would soar. A loaf of bread would cost a hundred euros. The consumption of meat would quickly be banned (George Church is himself a vegan), while cocaine would be legalized and promoted by governments to curb the appetite of younger generations and kill off the elderly.
“Hello, Professor, thank you for meeting with us. We’re currently on a world tour searching for immortality. Having already had our blood lasered, our iPS cells frozen, and our genomes sequenced, we wanted to know what other things we might do so that we can forever remain earthbound. From what I’ve heard, you study centenarians …?”
“We were originally studying a group of seventy people, all of whom are more than 110 years old, but we’ve opened up the panel to include people as young as 107: there are a lot of them. The oldest person in our group is 113—we celebrated his birthday here two weeks ago.”
“You bring them here?”
“No, no, we leave them exactly where they are! We sequence their DNA and look for some common element in their genome that might explain why they live to be so old.”
With his imposing white beard, Doctor Church looked like a cross between Ernest Hemingway and Benoît Bartherotte. He sized us up, this genetic mastermind faced with two dunces and a sleeping child; his gaze was not that of a snob, but rather that of an educator. All of these scientists had agreed to meet with me because they felt the need to share their extraordinary discoveries. To them, I was an outlet, a source of amusement.
“What we do is compare the DNA of these centenarians with that of people who age normally.”
“You mean dead people?”
“Not necessarily, but patients in whom the effects of age are clearly marked. Obviously, our control group of centenarians age, too, only much later. They have wrinkles, they look old just like anyone else … but they’re a hundred and ten years old.”
Léonore looked at him suspiciously. Church was not very different from Professor Antonarakis, except for the fact that he had a virtually unlimited budget with which to conduct any and every experiment that occurred to him. In the world of genetic research, this was infuriating. She teased, “Are you also studying animals with long life expectancies?”
“Yes, we’ve sequenced the genome of the bowhead whale, for example, which lives to be two hundred. We’ve also sequenced the naked mole-rat, which has a lifespan of thirty-one compared to the three-year lifespan of ordinary mice. The researcher I work with in Liverpool, João Pedro de Magalhães, is also studying capuchin monkeys, which have a lifespan much longer than other primates. What’s interesting is comparing long-lived species with related species that have a shorter lifespan. In doing so, we’ve managed to isolate a number of mutations that increase lifespan by a factor of ten. In the naked mole-rat, we have detected a DNA repair system that makes them all but immune to cancer.”
I hung on his every word. Here was the benefactor I had been searching for ever since I left Paris. In Lord of the Rings, a wizard called Gandalf holds the secret of eternal life. But he’s got a longer beard.
“You also work on a project with a fascinating name: Age Reversal. How can you reverse the process of aging and, assuming that you can, where do I sign up?”
“Certain life expectancies are extensive from the moment of birth, but actually, we’ve recently discovered systems that when introduced late in life can reverse aging.”
“Do you have a concrete example?”
“The mitochondrion is a miniscule but very important organelle,” he went on, “it is the powerhouse of the cell. It generates most of the cell’s supply of chemical energy and makes cellular respiration possible. We believe that it is oxidative stress in the mitochondria that causes us to age. If their DNA mutates, for example, we start to lose our hair. Scientists at the University of Tsukuba in Japan discovered that by adding glycine to mitochondria, a 97-year-old cell could be rejuvenated. And in December 2013, David Sinclair, one of our researchers here, successfully rejuvenated a two-year-old mouse muscle to six months by injecting it with NAD.”
“NAD? What’s that?”
“Nicotinamide adenine dinucleotide.”
“Gesundheit!”
“NAD facilitates communication between the mitochondria and the cell nucleus. At the human level, what my colleague has achieved is inestimable. It is the equivalent of rejuvenating someone of sixty to the age of twenty.”
“By Jove!” as they say in English. At this very moment, all across the planet, bio-geeks are experimenting with hundreds of extraordinary, incomprehensibly named substances in the search for age reversal. Biochemists are the modern equivalent of alchemists. But what the “Hemingway of the genome” had just calmly said had me jumping to my feet like the guy at a football match who starts the Mexican wave.
“NAD is the quintessence that Johannes de Rupescissa dreamed of when he wrote De consideratione quintae essentiae rerum omnium back in 1350! It’s the philosopher’s stone! The Holy Grail! The fountain of eternal youth! Gimme it now!”
“Calm down. It has been marketed by Elysium under the brand name ‘Basis’—it’s a dietary supplement. But the notion that we can just pop a pill to reverse aging is a little optimistic. I’d say gene therapy is at the opposite end of the spectrum: it’s complex and very expensive—about a million dollars for a single injection. If people could just take NAD orally, we’d already be living to be three hundred. The tests with Elysium are promising but, for the supplement to work, you’d have to take one every fifteen minutes because that’s how quickly it is eliminated from the body. You’d need to pop pills all day, and at night you’d need an alarm to wake you up every fifteen minutes. Alternatively, you could walk around with a pump that continuously injects NAD into your arm. So, you see, we start off with a natural process, but before long it becomes a form of slavery. It’s possible that we’ll find a
better way to use it. The advantage of using a gene is that it works constantly from within the body. Which seems like a better option.”
Church knew how to blow hot and cold. Maybe he had Scottish ancestors, like me? I liked his trousers. They were the trousers of a man who didn’t give a damn about trousers.
“The Yamanaka factors offer another possibility for cellular rejuvenation. I can reprogramme my cells to become stem cells using the four Yamanaka factors, and the 62-year-old cells will be identical to a baby’s cells. This is a genuine ‘reset.’ Last month, this process was successfully carried out for the first time on a live animal. The mice in the experiment were successfully rejuvenated. Their pancreatic cells were regenerated, their skin, their kidneys, their blood vessels, their stomach, their spine … We’ve also managed to reverse aging by what is pretentiously called ‘heterochronic parabiosis,’ a convoluted term for a simple process: take an old mouse and a young mouse and connect their circulatory systems. Blood flows between them. This significantly reverses aging in the older mouse.”
“Does that mean young blood is the fountain of youth?”
“Young blood not only rejuvenates the donor patient’s blood, but all his other organs. We detected regeneration in numerous parts of the older animal: heart, muscle tissue, the neural and vascular systems …”
“You’re reinforcing the old notion of vampirism. In the late sixteenth century, Countess Elizabeth Báthory drank the blood of virgins to stay young …”**
** (Food critic’s note) At l’Avant-Comptoir du Marché (on the corner of rue Lobineau / rue Mabillon in Paris) they serve shots of Béarn blood for €2.
“Her mistake was in ingesting the blood. It has to be transfused directly into the veins. Right now we’re trying to find out what it is about young blood that causes rejuvenation.”
“Why don’t you inject young blood into your supercentenarians?”
“My answer can be summed up by an acronym: DBPCRCT.”
“Pardon?”
Léonore laughed and translated for me: “It stands for Double Blind Placebo Randomized Controlled Clinical Trials. Before any therapy can be tested on a human being, we have to organize randomized clinical trials in which neither the patients nor the doctors know who is receiving the therapy, and who is taking a placebo.”
Their shared genetic in-jokes were starting to get on my non-genetically-rejuvenated nerves. It’s hardly my fault that when I was twenty I preferred wasting my nights at Chez Castel rather than undergoing ten years of medical training.
“It’s the only objective scientific methodology,” Church went on. “A lot of the therapies on the market are nothing more than snake oil. Anything that hasn’t undergone a double-blind trial is a scam, and with age reversal, there’s a serious temptation since your target market is … the whole of humanity. Here at the lab, we are looking at which genes slow down the aging process. Our supercentenarians have different genomes, but what would happen if we discovered they shared a common gene? We might be able to create a genome that would extend human life expectancy … or not. Right now, we’re testing purified and/or synthetic blood in mice. If it works, we’ll move on to dogs and only then to human patients. We’re looking for the right combination. And, with all these ideas, our eventual goal is to do DBPCRCT.”
“Where do you come up with your ideas? Is it luck, science, serendipity?”
“Ideas can come from everywhere, from books, from dreams … Sometimes we just pick a gene at random. But the important thing is the double-blind trial; that’s the only way to confirm age reversal. Just because a gene allows someone to live longer, that doesn’t mean it can reverse time, and that’s what we’re ultimately looking for.”
“Why are you focused on age reversal rather than simply prolonging life?”
“Because most of the humans in our market have already been born!”
Léonore laughed; I was afraid she might wake Lou, but the baby carried on snoring—a trait inherited from her father.
“The ethics on gene modification in the germline are very strict. It’s easier to get approval from the FDA (Food and Drug Administration) for genuine scientific research on rejuvenating than on extending human life expectancy. It’s a simple problem: finding out whether a pill extends life expectancy by fifteen years takes precisely fifteen years. There’s no way for me to prove that I’ve extended your life by fifteen years any faster. But, if I can come up with a therapy that rejuvenates you by fifteen years, we can see the effects immediately. Your face, your muscles, your organs will have changed.”
“This is the experiment carried out on mice here at Harvard in late 2016?”
“Yes. We took old mice and we fed them the Yamanaka factors according to a specific schedule (twice a week), diluted with an antibiotic (doxycycline). We were then able to determine age reversal by various factors: grip strength (we observe the mouse gripping a bar), swimming, intelligence tests (the mouse finds its way out of the maze more quickly), reflexes … and a thirty-percent increase in life expectancy. When we move on to dogs, we’ll do the same tests.”
“When will you start testing on human subjects?”
“At the moment, we’re testing forty or fifty different gene therapies. Those that work on mice will be tested on dogs. Getting clearance from the FDA to test on dogs is much faster than it is for on humans. (And we don’t need FDA approval to work with mice.) There are people with old dogs who are willing to pay to try to rejuvenate them. I think that within a year or so, we’ll start experiments on human subjects.”
“I can give you a long list of celebs who would be willing to pay a fortune not to die.”
Léonore seemed shocked by the strength of Church’s conviction. Having rubbed shoulders with one of the pioneers of genome sequencing, she should have been used to this kind of madness. But unlike Antonarakis’s thoughtful nature, Church’s charisma stemmed from something different: he had no taboos. This was both exhilarating and dizzying. Professor Church spoke unusually freely for someone who taught at such a high level (he holds professorships both at Harvard and at MIT). I continued the interview with a question that André Choulika had suggested to me: “And you could extend my telomeres?”***
*** (Author’s note) Telomeres are the caps at the end of each strand of DNA that protect chromosomes. They have sometimes been linked to aging.
“We know how to do it with mice. There is one human subject who’s received gene therapy to have her telomeres lengthened (the subject’s name appears sixteen lines down). We know how to increase the production of telomerase, the enzyme that lengthens telomeres. But you have to be careful because if you lengthen telomeres too much, it increases the risk of cancer. What works in mice is to strike a balance between extending telomeres, and anti-cancer action.”
“I’m confused. Which path should I choose if I want to live forever?”
“In my opinion, there are eight or nine different causes of aging. Telomere shortening is one, but the list also includes oxidation stress in mitochondria, the decline of cell renewal, blood, and so on. To combat aging means tackling eight or nine different processes that are probably interconnected. Not that we find the idea intimidating.”
“Isn’t gene therapy dangerous? Elizabeth Parrish, the CEO of BioViva, went to Colombia to have her DNA modified to lengthen her telomeres. In the media, she introduces herself as the first ‘upgraded’ woman. Isn’t she risking her life?”
“To go back to what I said before, everything has to go through a double-blind protocol if you want to avoid experiments that are unscientific. That said, like any therapy, genetic modification is considered hazardous until proven otherwise. I personally believe that genetic manipulation is not only harmless but helpful.”
“When will we know if genetically modified humans are viable?”
“The advantage of genome editing in age reversal is that you
see if it works immediately. But we can’t immediately tell whether there are no side effects. In general, the FDA approves therapies if they don’t cause serious side effects within the following year. That’s the rule: one year. To genetically reprogramme a human being, an edited gene has to be inserted into a virus that delivers it to the cells in the body, but in doing so we risk compromising our immune system …”
“Choulika uses T cells and the HIV virus. I’ve just had my genome sequenced and my iPS cells frozen. What is the next step on the road to eternity: getting myself injected with HIV?”
“When it comes to freezing, I prefer to freeze umbilical-cord cells. IPS cells are artificially created by powerful genes that can cause cancer. Freezing blood cells from the umbilical cord at birth is something I compare to having an airbag in your car: you’ll probably never need it, but it’s useful to have it just in case.”
Since he had dodged my question, I tried to be more precise.
“What do you think about 3D-printed organs?”
“It’s spectacular. We’re working here on printing organs, but I don’t think it’s the best technique. Errors creep in. It’s like a photocopy with a flaw, sometimes of only half a millimetre. I’d be worried about transplanting pixelated organs. Besides, it’s a slow process. You have to remember that the organ you’re trying to replace is dying, since it has to be surgically removed to be copied. In the meantime, the blood vessels are disconnected, and the printing process can take thousands of hours! Last but not least, it’s extremely expensive. The other approach is using developmental biology to grow human tissue in a laboratory. We’re already able to make human blood … We’ll publish a paper on that soon.”
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