Aubrey de Grey at the World Stem Cell Summit in Miami on January 25, 2018.
Aging is not a mystery, says famed researcher Dr. Aubrey de Grey, perhaps the world's foremost advocate of the provocative view that medical technology will one day allow humans to control the aging process and live healthily into our hundreds—or even thousands.
"The cultural attitudes toward all of this are going to be completely turned upside down by sufficiently promising results in the lab, in mice."
He likens aging to a car wearing down over time; as the body operates normally, it accumulates damage which can be tolerated for a while, but eventually sends us into steep decline. The most promising way to escape this biological reality, he says, is to repair the damage as needed with precise scientific tools.
The bad news is that doing this groundbreaking research takes a long time and a lot of money, which has not always been readily available, in part due to a cultural phenomenon he terms "the pro-aging trance." Cultural attitudes have long been fatalistic about the inevitability of aging; many people balk at the seemingly implausible prospect of indefinite longevity.
But the good news for de Grey—and those who are cheering him on—is that his view is becoming less radical these days. Both the academic and private sectors are racing to tackle aging; his own SENS Research Foundation, for one, has spun out into five different companies. Defeating aging, he says, "is not just a future industry; it's an industry now that will be both profitable and extremely good for your health."
De Grey sat down with Editor-in-Chief Kira Peikoff at the World Stem Cell Summit in Miami to give LeapsMag the latest scoop on his work. Here is an edited and condensed version of our conversation.
Since your book Ending Aging was published a decade ago, scientific breakthroughs in stem cell research, genome editing, and other fields have taken the world by storm. Which of these have most affected your research?
They have all affected it a lot in one way, and hardly at all in another way. They have speeded it up--facilitated short cuts, ways to get where we're already trying to go. What they have not done is identified any fundamental changes to the overall strategy. In the book, we described the seven major types of damage, and particular ways of going about fixing each of them, and that hasn't changed.
"Repair at the microscopic level, one would be able to expect to do without surgery, just by injecting the right kind of stem cells."
Has any breakthrough specifically made the biggest impact?
It's not just the obvious things, like iPS (induced pluripotent stem cells) and CRISPR (a precise tool for editing genes). It's also the more esoteric things that applied specifically to certain of our areas, but most people don't really know about them. For example, the identification of how to control something called co-translational mitochondrial protein import.
How much of the future of anti-aging treatments will involve regeneration of old tissue, or wholesale growth of new organs?
The more large-scale ones, regenerating whole new organs, are probably only going to play a role in the short-term and will be phased out relatively rapidly, simply because, in order to be useful, one has to employ surgery, which is really invasive. We'll want to try to get around that, but it seems quite likely that in the very early stages, the techniques we have for repairing things at the molecular and cellular level in situ will be insufficiently comprehensive, and so we will need to do the more sledgehammer approach of building a whole new organ and sticking it in.
Every time you are in a position where you're replacing an organ, you have the option, in principle, of repairing the organ, without replacing it. And repair at the microscopic level, one would be able to expect to do without surgery, just by injecting the right kind of stem cells or whatever. That would be something one would expect to be able to apply to someone much closer to death's door and much more safely in general, and probably much more cheaply. One would expect that subsequent generations of these therapies would move in that direction.
Your foundation is working on an initiative requiring $50 million in funding—
Well, if we had $50 million per year in funding, we could go about three times faster than we are on $5 million per year.
And you're looking at a 2021 timeframe to start human trials?
That's approximate. Remember, because we accumulate in the body so many different types of damage, that means we have many different types of therapy to repair that damage. And of course, each of those types has to be developed independently. It's very much a divide and conquer therapy. The therapies interact with each other to some extent; the repair of one type of damage may slow down the creation of another type of damage, but still that's how it's going to be.
And some of these therapies are much easier to implement than others. The easier components of what we need to do are already in clinical trials—stem cell therapies especially, and immunotherapy against amyloid in the brain, for example. Even in phase III clinical trials in some cases. So when I talk about a timeframe like 2021, or early 20s shall we say, I'm really talking about the most difficult components.
What recent strides are you most excited about?
Looking back over the past couple of years, I'm particularly proud of the successes we've had in the very most difficult areas. If you go through the 7 components of SENS, there are two that have absolutely been stuck in a rut and have gotten nowhere for 15 to 20 years, and we basically fixed that in both cases. We published two years ago in Science magazine that essentially showed a way forward against the stiffening of the extracellular matrix, which is responsible for things like wrinkles and hypertension. And then a year ago, we published a real breakthrough paper with regard to placing copies of the mitochondria DNA in the nuclear DNA modified in such a way that they still work, which is an idea that had been around for 30 years; everyone had given up on it, some a long time ago, and we basically revived it.
A slide presented by Aubrey de Grey, referencing his collaboration with Mike West at AgeX, showing the 7 types of damage that he believes must be repaired to end aging.
(Courtesy Kira Peikoff)
That's exciting. What do you think are the biggest barriers to defeating aging today: the technological challenges, the regulatory framework, the cost, or the cultural attitude of the "pro-aging" trance?
One can't really address those independently of each other. The technological side is one thing; it's hard, but we know where we're going, we've got a plan. The other ones are very intertwined with each other. A lot of people are inclined to say, the regulatory hurdle will be completely insurmountable, plus people don't recognize aging as a disease, so it's going to be a complete nonstarter. I think that's nonsense. And the reason is because the cultural attitudes toward all of this are going to be completely turned upside down before we have to worry about the regulatory hurdles. In other words, they're going to be turned upside down by sufficiently promising results in the lab, in mice. Once we get to be able to rejuvenate actually old mice really well so they live substantially longer than they otherwise would have done, in a healthy state, everyone's going to know about it and everyone's going to demand – it's not going to be possible to get re-elected unless you have a manifesto commitment to turn the FDA completely upside down and make sure this happens without any kind of regulatory obstacle.
I've been struggling away all these years trying to bring little bits of money in the door, and the reason I have is because of the skepticism as to regards whether this could actually work, combined with the pro-aging trance, which is a product of the skepticism – people not wanting to get their hopes up, so finding excuses about aging being a blessing in disguise, so they don't have to think about it. All of that will literally disintegrate pretty much overnight when we have the right kind of sufficiently impressive progress in the lab. Therefore, the availability of money will also [open up]. It's already cracking: we're already seeing the beginnings of the actual rejuvenation biotechnology industry that I've been talking about with a twinkle in my eye for some years.
"For humans, a 50-50 chance would be twenty years at this point, and there's a 10 percent chance that we won't get there for a hundred years."
Why do you think the culture is starting to shift?
There's no one thing yet. There will be that tipping point I mentioned, perhaps five years from now when we get a real breakthrough, decisive results in mice that make it simply impossible to carry on being fatalistic about all this. Prior to that, what we're already seeing is the impact of sheer old-school repeat advertising—me going out there, banging away and saying the same fucking thing again and again, and nobody saying anything that persuasively knocks me down. … And it's also the fact that we are making incremental amounts of progress, not just ourselves, but the scientific community generally. It has become incrementally more plausible that what I say might be true.
I'm sure you hate getting the timeline question, but if we're five years away from this breakthrough in mice, it's hard to resist asking—how far is that in terms of a human cure?
When I give any kind of timeframes, the only real care I have to take is to emphasize the variance. In this case I think we have got a 50-50 chance of getting to that tipping point in mice within five years from now, certainly it could be 10 or 15 years if we get unlucky. Similarly, for humans, a 50-50 chance would be twenty years at this point, and there's a 10 percent chance that we won't get there for a hundred years.
"I don't get people coming to me saying, well I don't think medicine for the elderly should be done because if it worked it would be a bad thing. People like to ignore this contradiction."
What would you tell skeptical people are the biggest benefits of a very long-lived population?
Any question about the longevity of people is the wrong question. Because the longevity that people fixate about so much will only ever occur as a side effect of health. However long ago you were born or however recently, if you're sick, you're likely to die fairly soon unless we can stop you being sick. Whereas if you're healthy, you're not. So if we do as well as we think we can do in terms of keeping people healthy and youthful however long ago they were born, then the side effect in terms of longevity and life expectancy is likely to be very large. But it's still a side effect, so the way that people actually ought to be—in fact have a requirement to be—thinking, is about whether they want people to be healthy.
Now I don't get people coming to me saying, well I don't think medicine for the elderly should be done because if it worked it would be a bad thing. People like to ignore this contradiction, they like to sweep it under the carpet and say, oh yeah, aging is totally a good thing.
People will never actually admit to the fact that what they are fundamentally saying is medicine for the elderly, if it actually works, would be bad, but still that is what they are saying.
Shifting gears a bit, I'm curious to find out which other radical visionaries in science and tech today you most admire?
Fair question. One is Mike West. I have the great privilege that I now work for him part-time with Age X. I have looked up to him very much for the past ten years, because what he did over the past 20 years starting with Geron is unimaginable today. He was working in an environment where I would not have dreamt of the possibility of getting any private money, any actual investment, in something that far out, that far ahead of its time, and he did it, again and again. It's insane what he managed to do.
What about someone like Elon Musk?
Sure, he's another one. He is totally impervious to the caution and criticism and conservatism that pervades humanity, and he's getting on making these bloody self-driving cars, space tourism, and so on, making them happen. He's thinking just the way I'm thinking really.
"You can just choose how frequently and how thoroughly you repair the damage. And you can make a different choice next time."
You famously said ten years ago that you think the first person to live to 1000 is already alive. Do you think that's still the case?
Definitely, yeah. I can't see how it could not be. Again, it's a probabilistic thing. I said there's at least a 10 percent chance that we won't get to what I call Longevity Escape Velocity for 100 years and if that's true, then the statement about 1000 years being alive already is not going to be the case. But for sure, I believe that the beneficiaries of what we may as well call SENS 1.0, the point where we get to LEV, those people are exceptionally unlikely ever to suffer from any kind of ill health correlated with their age. Because we will never fall below Longevity Escape Velocity once we attain it.
Could someone who was just born today expect—
I would say people in middle age now have a fair chance. Remember – a 50/50 chance of getting to LEV within 20 years, and when you get there, you don't just stay at biologically 70 or 80, you are rejuvenated back to biologically 30 or 40 and you stay there, so your risk of death each year is not related to how long ago you were born, it's the same as a young adult. Today, that's less than 1 in 1000 per year, and that number is going to go down as we get self-driving cars and all that, so actually 1000 is a very conservative number.
So you would be able to choose what age you wanted to go back to?
Oh sure, of course, it's just like a car. What you're doing is you're repairing damage, and the damage is still being created by the body's metabolism, so you can just choose how frequently and how thoroughly you repair the damage. And you can make a different choice next time.
What would be your perfect age?
I have no idea. That's something I don't have an opinion about, because I could change it whenever I like.
Recent immigration restrictions have left many foreign researchers' projects and careers in limbo—and some in jeopardy.
"I spent about $4,000 on lawyer fees and another $1,200 to pay for the motions I filed," she recalls. "I had to borrow money from my parents and my cousin because without my salary I just didn't have the $7,000 at hand." But the already narrow window of opportunity slammed completely shut when the Trump administration suspended issuing new visas for foreign researchers in June. All Mohan's attempts were denied. In August, she had to leave the country. "Given the recent work visa ban by the administration, all my options in the U.S. are closed," she wrote a bitter note on Twitter. "I have to uproot my entire life in NY for the past 6 years and leave." She eventually found a temporary position in Calcutta, where she can continue research.
Mohan is hardly alone in her visa saga. Many foreign scholars on H- and J-type visas and other permits that let them remain employed in America had been struggling to keep their rights to continue research, which in certain cases is crucial to battling the pandemic. Some had to leave the country, some filed every possible extension to buy time, and others are stuck in their home countries, unable to return. The already cumbersome process of applying for visas and extensions became crippled during the lockdowns. But in June, when President Trump extended and expanded immigration restrictions to cut the number of immigrant workers entering the U.S., the new limits left researchers' projects and careers in limbo—and some in jeopardy.
"We have been a beneficiary of this flow of human capacity and resource investment for many generations—and this is now threatened."
Rakesh Ramachandran, whose computational biology work contributed to one of the first coronavirus studies to map out its protein structures—is stranded in India. In early March, he had travelled there to attend a conference and visit the American consulate to stamp his H1 visa for a renewal, already granted. The pandemic shut down both the conference and the consulates, and Ramachandran hasn't been able to come back since. The consulates finally opened in September, but so far the online portal has no available appointment slots. "I'm told to keep trying," Ramachandran says.
The visa restrictions affected researchers worldwide, regardless of disciplines or countries. A Ph.D. student in neuroscience, Morgane Leroux had to do her experiments with mice at Gladstone Institutes in America and analyze the data back home at Sorbonne University in France. She had finished her first round of experiments when the lockdowns forced her to return to Paris, and she hasn't been able to come back to resume her work since. "I can't continue the experiments, which is really frustrating," she says, especially because she doesn't know what it means for her Ph.D. "I may have to entirely change my subject," she says, which she doesn't want to do—it would be a waste of time and money.
But besides wreaking havoc in scholars' personal lives and careers, the visa restrictions had—and will continue to have—tremendous deleterious effects on America's research and its global scientific competitiveness. "It's incredibly short-sighted and self-destructing to restrict the immigration of scientists into the U.S.," says Benjamin G. Neel, who directs the Laura and Isaac Perlmutter Cancer Center at New York University. "If they can't come here, they will go elsewhere," he says, causing a brain drain.
Neel in his lab with postdocs
(Courtesy of Neel)
Neel felt the outcomes of the shortsighted policies firsthand. In the past few months, his lab lost two postdoctoral researchers who had made major strides in understanding the biology of several particularly stubborn, treatment-resistant malignancies. One postdoc studied the underlying mechanisms responsible for 90 percent of pancreatic cancers and half of the colon ones. The other one devised a new system of modeling ovarian cancer in mice to test new therapeutic drug combinations for the deadliest tumor types—but had to return home to China.
"By working around the clock, she was able to get her paper accepted, but she hasn't been able to train us to use this new system, which can set us back six months," Neel says.
Her discoveries also helped the lab secure about $900,000 in grants for new research. Losing people like this is "literally killing the goose that lays the golden eggs," Neel adds. "If you want to make America poor again, this is the way to do it."
Cassidy R. Sugimoto at Indiana University Bloomington, who studies how scientific knowledge is produced and disseminated, says that scientists are the most productive when they are free to move, exchange ideas, and work at labs with the best equipment. Restricting that freedom reduces their achievement.
"Several empirical studied demonstrated the benefits to the U.S. by attracting and retaining foreign scientists. The disproportional number of our Nobel Prize winners were not only foreign-born but also foreign-educated," she says. Scientific advancement bolsters the country's economic prowess, too, so turning scholars away is bad for the economy long-term. "We have been a beneficiary of this flow of human capacity and resource investment for many generations—and this is now threatened," Sugimoto adds—because scientists will look elsewhere. "We are seeing them shifting to other countries that are more hospitable, both ideologically and in terms of health security. Many visiting scholars, postdocs, and graduate students who would otherwise come to the United States are now moving to Canada."
It's not only the Ph.D. students and postdocs who are affected. In some cases, even well-established professors who have already made their marks in the field and direct their own labs at prestigious research institutions may have to pack up and leave the country in the next few months. One scientist who directs a prominent neuroscience lab is betting on his visa renewal and a green card application, but if that's denied, the entire lab may be in jeopardy, as many grants hinge on his ability to stay employed in America.
"It's devastating to even think that it can happen," he says—after years of efforts invested. "I can't even comprehend how it would feel. It would be terrifying and really sad." (He asked to withhold his name for fear that it may adversely affect his applications.) Another scientist who originally shared her story for this article, later changed her mind and withdrew, worrying that speaking out may hurt the entire project, a high-profile COVID-19 effort. It's not how things should work in a democratic country, scientists admit, but that's the reality.
Still, some foreign scholars are speaking up. Mehmet Doğan, a physicist at University of California Berkeley who has been fighting a visa extension battle all year, says it's important to push back in an organized fashion with petitions and engage legislators. "This administration was very creative in finding subtle and not so subtle ways to make our lives more difficult," Doğan says. He adds that the newest rules, proposed by the Department of Homeland Security on September 24, could further limit the time scholars can stay, forcing them into continuous extension battles. That's why the upcoming election might be a turning point for foreign academics. "This election will decide if many of us will see the U.S. as the place to stay and work or whether we look at other countries," Doğan says, echoing the worries of Neel, Sugimoto, and others in academia.
Dogan on Zoom talking to his fellow union members of the Academic Researchers United, a union of almost 5,000 Academic Researchers.
(Credit: Ceyda Durmaz Dogan)
If this year has shown us anything, it is that viruses and pandemics know no borders as they sweep across the globe. Likewise, science can't be restrained by borders either. "Science is an international endeavor," says Neel—and right now humankind now needs unified scientific research more than ever, unhindered by immigration hurdles and visa wars. Humanity's wellbeing in America and beyond depends on it.
[Editor's Note: To read other articles in this special magazine issue, visit the beautifully designed e-reader version.]