Article 64Y20 The bird is fine, the bird is fine, the bird is fine, it’s dead.

The bird is fine, the bird is fine, the bird is fine, it’s dead.

by
Jonathan Weiner
from MIT Technology Review on (#64Y20)
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Twenty years have passed since I first met Aubrey de Grey, the man with the Methuselah beard. Back then he was already a True Believer in the quest for immortality. But he wasn't famous, or notorious, yet; he wasn't Aubrey!, as he would soon become to his fans in the anti-aging crowd. And he wasn't yet a man in disgrace.

In those days he worked as a computer programmer in the Department of Genetics at the University of Cambridge, in England. On the side he was trying to break into the aging field, which was still small. Most of the scientists who worked in it-gerontologists-wished he would go away. They wanted to give people just a few more healthy years. The last thing they needed was a Methuselah-or Rasputin-look-alike at their conferences, a fast-talking outsider who drank beer from morning to night and claimed we could live for more than 1,000 years. The science of longevity had enough of a credibility problem as it was.

I'm riffling through the pages of my last book, Long for This World, to find the scene where we met. It was a bright morning in March of 2002. I picked Aubrey up at the airport in Philadelphia and drove him to the town in Pennsylvania where I lived at the time. Over the next few days of interviews in my study, while he tried to convince me that science can and should end aging, we often trooped down the stairs to the kitchen so that he could fortify himself with another beer. When my two sons bumped into us by the refrigerator, Aubrey took his sales pitch from the top and told them they had a good chance to live for centuries, or millennia, or maybe longer if they were lucky. The boys were teenagers back then, 14 and 17. They already felt immortal. They liked meeting a grownup who knew it was true.

Right. Now those two boys are in their 30s, and I can see 70 coming fast.

Just flipping through these pages (they're 12 years old and already showing their age-definitely not acid-free paper) is making me cranky. Even skimming them makes me feel like a horrible curmudgeon. I was not a convert back then. Nor am I today. But a True Believer like Aubrey is always convinced that he will win you over if he gives his pitch just one more try; and here he is, in scene after scene, trying again. On top of all the usual writer's regrets, revisiting the science of eternal youth is making me feel old.

If high intelligence is the ability to hold two opposing ideas in our heads at the same time, then most of us are geniuses about aging a few times over. We think it will never come for us. We think it might come but it will stop before it reaches us. We think it's coming and there is absolutely nothing we can do about it.

It was the great molecular biologist Seymour Benzer who got me interested in the idea that aging might be malleable. Benzer was a night owl. I was writing a book about him, and in the late 1990s he used to talk about aging in his Fly Room at Caltech in a hushed, conspiratorial voice, even though it was just the two of us and a thousand fly bottles at three in the morning. I'll never forget how startling it was to hear a serious scientist say, We might be able to do something about this.

Nor was he the only one to say it. At the University of California, San Francisco, Cynthia Kenyon was dissecting the aging of the worm C. elegans. In 1993, she had announced the discovery of a mutant that lived about twice as long as the average C. elegans and looked young and sleek almost to the end. At MIT, Lenny Guarente was dissecting the genetics of aging in yeast, and he seemed to be getting somewhere too. In 1998, when Benzer was 77 years old, he announced the discovery of a mutant fruit fly he called Methuselah. It could live for 100 days. The average fly in his bottles died at around 60.

I'll never forget how startling it was to hear a serious scientist say, We might be able to do something about this."

Versions of many of those same fly, worm, and yeast genes are found in every animal under the sun, including us. By starting with those first few so-called longevity genes and tracing their connections, molecular biologists could study the workings of the clock, so to speak. Someday they could hope to slow down the hands.

On that hope, or hypothesis-which is still only a hypothesis today-the aging field exploded. In 1999, one year after Benzer's Methuselah, Guarente and Kenyon cofounded Elixir Pharmaceuticals. They planned to explore and exploit sirtuins-proteins that are involved in the process of aging, among other things. In 2004, Guarente's former student David Sinclair cofounded Sirtris Pharmaceuticals to race against Elixir. In 2013, Google started the R&D company Calico, with a budget that was rumored to be in the hundreds of millions. Kenyon is Calico's vice president of aging research.

Smart new talent poured into the field, including the prodigy Laura Deming. She became fascinated by the biology of aging at the age of eight, as a homeschooler in New Zealand. Her grandmother had come to visit, and Laura was sad to see how much she suffered from her arthritic joints. At 12, she joined Kenyon's lab at UCSF. At 14, she was accepted at MIT. A few years later, she dropped out of college to launch her career as a venture capitalist. She founded the Longevity Fund. According to its website, Longevity Fund companies have now raised more than $1 billion.

Today there are almost too many anti-aging startups and foundations to count. Each one is trying to leverage some of the latest tools in biomedicine-CRISPR, AI, Yamanaka factors, epigenetics, proteomics, metabolomics-and slow down the hands of that clock. Last December it was NewLimit, with more than $100 million in funding from the Coinbase billionaire Brian Armstrong. This past January it was Altos Labs, with $3 billion in funding; one of its investors is rumored to be Jeff Bezos. The Hevolution Foundation, which was started by the royal family of Saudi Arabia, has plans to spend $1 billion a year on the search for ways to slow aging.

Meanwhile, Aubrey de Grey kept banging the drum for the cause. Within what felt like five minutes after our first meeting in 2002, he became a secular guru, a prophet of immortality-to the intense annoyance of most of the scientists in the aging field. He cofounded the Methuselah Foundation and the SENS Research Foundation to sponsor research, education, and conferences and help speed things up. SENS" refers to his own plan for ending aging: strategies for engineered negligible senescence." This is the scheme he explained to me back in my old study 20 years ago. If we just fix Seven Deadly Things, our bodies will survive long enough for further advances in medical science to come along in a timely fashion and keep us alive forever. Those Seven Deadly Things include, for instance, cancer. Just cure cancer.

When the cryptocurrency crowd got interested in anti-aging science a couple of years back, many of them liked the sound of SENS. In the summer of 2021, a new crypto system called PulseChain raised $25 million worth of cryptocurrency in two weeks for the SENS Research Foundation. The foundation had always been small and a bit fringy, just bumping along; this was by far the biggest windfall in its history.

But at about the same time that the PulseChain gift rolled in, the SENS board fired Aubrey. Celine Halioua, the young founder and CEO of Loyal, a biotech firm that hopes to lengthen the life spans of dogs, had accused him of being a sexual predator. So had Laura Deming, the founder of the Longevity Fund. Deming wrote in a blog post:

I've decided not to work with Aubrey de Grey or SENS in any capacity moving forward.

I had one bad experience with him when I was 17-he told me in writing that he had an adventurous love life' and that it had always felt quite jarring' not to let conversations with me stray in that direction given that [he] could treat [me] as an equal on every other level'.

He sent this from his work email, and I'd known him since I was 14 ...

I've learned it's a serial pattern he's enacted with women over whom he's in a position of power ...

I almost left the field several times as a teenager because of stuff like this happening.

Deming hasn't answered my emails requesting an interview. I've spoken with Halioua, who is happy to talk about her hopes for Loyal but would rather not comment about Aubrey. On her website, she writes, For years he has used his position of power in the aging field to attract his victims. These victims include me, Laura Deming, and multiple other anonymous women." She mentions harassment by another SENS executive and says that every dollar that goes to Aubrey holds back the field."

Aubrey denied the accusations. He said he would fight the SENS board over his dismissal. By then he was so well known, and the quest for the Fountain of Youth so highly charged, that the scandal made headlines in the science press.

Back when the science of aging was still a backwater, I thought it was a good idea to explore the field, in all its ambiguities and contradictions, by talking skeptically with an immortalist like de Grey. Now, two decades later and myself two decades older, with so much hype and money flying around, I'd rather hang with the realists.

Lately I've been calling a few gerontologists to check in. Just saying hi, we can feel how much time has passed since we last spoke. Even our voices have aged. And what a time this is to be an aging mortal. A surprising number of scientists couldn't talk at all, because they were dealing with family medical emergencies.

I called Daniel Promislow, one of the directors of the Dog Aging Project, a massive study that may soon be teaching new tricks in veterinary and human clinics. I called Steve Austad, a senior gerontologist, who thinks we can also learn lessons from the life spans and health spans of birds. Many species of birds seem to stay fit and even fertile until very close to the end. Vets have a saying," Austad told me. The bird is fine, the bird is fine, the bird is fine, it's dead.'"

I called James Kirkland, a doctor at the Mayo Clinic. Kirkland is conducting a series of early-stage clinical trials of senolytics, experimental new drugs that attack and kill senescent cells, which seem to be fundamental to the aging process. These are very early days for senolytics, Kirkland emphasized. The drugs may or may not turn out to be safe; if they are safe, they may or may not work; even if they work, they won't make anyone live to 120. That's not what his patients are looking for anyway, he said. They just want help with their osteoarthritis, their chronic kidney disease, their macular degeneration.

Most of these trials are going to fail, Kirkland said. Most trials do. People should try to be dispassionate, even though everyone has a stake in this game. I mean, every living person does."

I called the biologist Martin Raff, who retired from University College London 20 years ago, when he was not quite 65. Among other things, Raff had worked on cellular senescence. He told me that after a long and lucky life, he feels ready to depart.

Today the field that Benzer foresaw in his Fly Room in the last century is being taken seriously not only on Wall Street and in Silicon Valley and Riyadh but also at the National Institutes of Health. It's beginning to look more like a normal branch of research medicine, just one more plausible program to pursue.

The idea, of course, is to add good years to our lives without drawing out the number of bad years at the end.

The study of the clock really may teach us ways to slow down some of the fundamental deterioration we call aging, to treat whatever it is that leaves our bodies increasingly vulnerable to chronic diseases as we get older-senescent cells, for instance. If we can do that, according to what is known as the geroscience hypothesis, we can fight all those chronic diseases at once: arthritis, atherosclerosis, cancer, deafness, dementia, diabetes, osteoporosis, stroke.

The idea, of course, is to add good years to our lives without drawing out the number of bad years at the end. This is called the compression of morbidity. No one knows if it can be done, so the compression of morbidity is really a hypothesis on top of a hypothesis. Still, that is what most centenarians are able to do. They stay healthy two or three decades longer than the rest of us, and many of them feel quite well at the age of 100. The bird is fine, the bird is fine, the bird is fine, it's dead."

But we're all still mortals, and our kind will be mortal for a long, long time.

I Zoomed with a Canadian writer and academic I know, Andy Stark, author of The Consolations of Mortality. Maybe it's just sour grapes, Andy told me, but he thinks we are actually better off being mortal. His book explores many of the drawbacks of eternal life, including the terrible problem of boredom. How many times would you really want to ride the roller coaster? In Long for This World, I look at other problems, too, including the sixth extinction-the planetary catastrophe that is unfolding around us, inflicted by the fulfillment of so many human wishes. How much of that disaster would you really want to watch?

A few years ago, Andy Stark gave a talk at a symposium about the science of longevity. Aubrey de Grey was in the audience. When Andy was done, Aubrey strode up to the stage and challenged him. If I offered you an extra 30 healthy years, Aubrey said, you'd take that, wouldn't you? And after that, wouldn't you take the next 30 years, and the next 30? And so on?

Andy stood his ground, and he was right. There is an infinite difference between a few more years of healthy life and eternal life.

I called Aubrey, too. He lives on the edge of Silicon Valley now. He sounded more optimistic than ever. He was planning a sort of comeback conference in Dublin, a good place for beer. He's coined a word, the Methuselarity. That's the moment when medicine will be so advanced that we can more or less stop aging. He now thinks there's a 50% chance that the Methuselarity is 15 years away. That's pretty good," he said. I used to say it was 25 years away."

Q: How do you feel about mortality personally, all these years on?

A: Well, I seem to be doing okay. Not showing any signs of aging ...

Since we were Zooming, I could see that that was no truer for Aubrey than it is for me.

But I've always done this for humanitarian reasons," he said, just as he used to say 20 years ago. After all, aging ends tens of millions of lives each year. Whether the Methuselarity comes soon enough to save Aubrey himself is immaterial.

What about you?" he asked.

Well, Aubrey, I'm 10 years older than you are. I'm reconciling myself to being mortal. I'm looking for the consolations of mortality."

He rolled his eyes.

We'd had this argument so many times before that I quit scribbling down our words.

He said, You'd take a pill that gave you 10 more good years, if I offered it to you now ...

(My older son is still very much in the immortality camp. It pains and angers him that I would spurn a project that could bring us near-infinite rewards. To him it looks as if I am giving up on life itself.)

Seymour Benzer would not have liked how crowded the aging field has become. He was drawn to it partly because it was small. Once a new science got established, with rafts of research to follow, journals to keep up with, conferences to attend, he felt he no longer had the space to think. He moved on to something else.

For more than 60 years, the span of his long career, that strategy worked to stave off boredom. He was one of those mortals who show you how rich a finite life can be. In his 20s, his work in physics helped lead to the invention of the transistor. In his 30s and 40s, his work on the fine structure of the gene helped launch molecular biology. Then it was neurogenetics. Then the modern science of aging-along with much else. Even in his old age, he radiated curiosity: always the next field, the next experiment. I'd take a pill for that.

Benzer died from a stroke in November of 2007, at Huntington Hospital in Pasadena, California, at the age of 86. I heard from his family and friends that he worked cheerfully in his lab right to the end. At the hospital, just before he slid into a coma, he was still alert enough to look at the doctors and say, I have two questions ..."

And that was all.

Jonathan Weiner is a writer based in New York City. He won a National Book Critics Circle Award in 1999 for Time, Love, Memory, his book about Seymour Benzer. He teaches at Columbia Journalism School.

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