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Yes, we will increase our lifespan
An interview with David Gobel, founder of The Methuselah Foundation.
The Methuselah Foundation is a funding entity for health and longevity research that plans to “make 90 the new 50 by 2030,” and there are several ways they plan on accomplishing this.
Funded by their first venture, the 3D bioprinting company Organovo which went public in 2012, the companies in the organization’s portfolio aim to cure cancers, decrease cognitive impairments, reverse atherosclerosis, remediate Alzheimer’s―even 3D print mini livers, kidneys, and intestines.
I spoke with the organization’s founder, David Gobel, about how humans might be able to live to 120 and beyond. If this conversation isn’t enough to inspire many a science fiction novel, I don’t know what is.
Here is our interview in full. (Edited for clarity.)
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What is your ultimate mission with The Methuselah Foundation?
To extend the healthy human lifespan—no one wants to live an extra 50 years as a 120-year-old person who’s lost their marbles.
What do you think the healthy human lifespan could lengthen to?
If things are good today, why wouldn't we want a tomorrow? So I would say, “indefinite lifespan” might be the best way to put it, and that's the way it is today. In 1900, if you were 40 you were getting past your expiration date. Today, if you're at 80 you’re getting past your expiration date. So why not 120? If you're already 80, maybe in the next 40 years, if you could hang on, you would be able to jump to the next lily pad.
I’ve spoken to neurologists who believe the brain can’t hang on until 120
There are approximately 300 people on this planet who are already 110 years old and older. That’s just a statistical estimation—if you were to go to the Guinness Book of World Records, and look up Robert Young, he is a volunteer demographer that the Guinness Book of World Records uses to validate honest-to-god real supercentenarians as they're called.
I think it is fair to say that, since there are a nontrivial, but also very small number of people who achieve 110 years, then we know that humans can do that. Why not work toward being healthy along the way? I don't see anything wrong with that from an engineering standpoint, or from a medical standpoint. Almost all of the folks who are advanced in years, the thing they fear more than anything is being a burden. So they would happily contribute.
How did you get into this work?
I was one of the first folks who founded a company that did shared virtual worlds with avatars over the internet. But when I was 45, I decided I hated work and I wanted to retire. I hit an inflection point where, as an entrepreneur, I achieved a fairly nice payout and I did retire for six years and spent a lot of time with my family. But by the time four years were over, I was losing my mind. And by the time six years was up, I went back to work because I wanted to—I needed to.
I noticed that a lot of my friends, who were of a generation or two ahead of me, were bravely suffering the inevitable decline of their lives—they were dying, leaving big holes in their families, suffering from cancer, and getting Alzheimer's. And I thought to myself, that's really stupid, and it stinks, and unlike an airplane falling out of the sky that makes great TV at 11, it happens every day and everyone expects it to happen.
You are just expected to have a stiff upper lip and be miserable along the way and bankrupt nations while you're on your way out because the last two years of your life are so expensive and miserable. And I thought, you know, I've got probably another 20 years in me, why don't I see what we can do about that. It's impossible, it's ridiculous, it'll never happen, but what the heck, let's give it a try. That was 22 years ago.
I established Methuselah in 2000, incorporated it in 2001. At the same time, I went to work for the United States government after 9/11, in May of 2002. So I basically got two jobs. The way I thought of it is: I want to protect my 12-year-old daughter—that's what she was at that time—and if I can protect her, I'll protect everybody's 12-year-old daughter. That job gave me the opportunity, in my spare time, to develop Methuselah into a going concern, which took about seven years.
Funding longevity research has been a huge challenge, how did you do it?
I hate begging. And I hate nonprofits that seem to never actually do what they say they're going to do but are really good at continuing to ask for money.
So while I was in my entrepreneurial life, and then later in the government, I was rather involved with venture capital and incubators, having had some influence in starting the incubation movement in the mid-90s. And I thought, at some point, the technologies that were given grants to start up will need to turn into companies. So why don't we start a subsidiary to our foundation that is a for-profit investment-making vehicle?
We did that in 2007—that’s when we incorporated Methuselah Life Science Fund. Then in 2009, we invested in a company called Organovo, which is now a public company. The thesis of the for-profit is we would invest in mission driven companies, companies that would help accomplish our mission. Then, when they went public or had a liquidity event, we would be able to sell our stock and return that to the Foundation, which would then start more companies and issue more grants. Think of it as a positive ascending spiral.
Happily, that's what happened. We got 43 times our original investment in Organovo and that helped us start another four companies. Right now, our portfolio is 10 or 11 companies in epigenomic reprogramming, senescence cell ablation, mild cognitive impairment and potentially Alzheimer's remediation, reversal of atherosclerosis, and removal of cancer in 96 hours after treatment for melanoma, prostate, and as far as I can tell, pretty much most cancers.
Also using 3D tissue printing to create mini livers, mini kidneys, and mini intestines—while being able to test on human tissue, not derived from actual humans but printed so that the constructs, let's say the kidney, recapitulates with high fidelity the actual architecture of a kidney. It's not just a tissue blob with kidney cells, it's actually a very tiny kidney. And then you can test chemistry against those constructs, and they will react the way real human kidneys react. Our purpose there is to take animal testing out of the picture by 2030, maybe 2035, depending on the regulatory climate.
Why do we need to test human tissues, not animals?
Ninety-five percent of all drugs that work in experimental mouse models end up not working in humans. Were you aware of that? Think about the current medical research establishment as having a 55-gallon barrel drum into which you pour $100 bills, and then when you're done with that you put gasoline on top and light it—that's how effective it is. We've tested drugs that went all the way through the FDA approval process and got to market and then were found to be causing heart attacks or liver failures.
Whereas using human tissues—and even today we're at about an 85 percent success rate—we go ahead and test those [failures] on our constructs and, in each case, they show that we would have known a decade earlier that they weren't going to work.
There are drugs that are very effective with humans, that will kill animals. So what happens if you try something on a mouse and it kills the mouse and you decide, oh, I won't be able to take this forward and test it because it's already killed our model animal? I have no idea how many of those drugs, those chemistries, actually may have made a huge difference for humans, but they never went further.
And then finally, I don't like killing animals if you don't need to. It's still a necessity for medical research these days, but I look forward to a time where this early development and research that we're doing, and others are doing, will lead to the elimination of animal model testing.
Tell me more about tissue printing and why it’s important
One of our portfolio companies is Viscient, and the other one is Organovo. And they're both working on using human 3D tissue constructs to validate chemistries for intestine, irritable bowel syndrome, and other unannounced targets. And then we started a company called Volumetric which makes the world's highest resolution tissue printer.
If you think about an inkjet printer, you would have a cartridge of ink, right? And that ink would be electrostatically aimed at the paper under control of the computer. As it's being pulled out of the cartridge, it turns into microscopic drops and those drops end up hitting the paper and forming a letter. Now, instead of moving to the next letter, what if you let that letter “A,” dry and then you did another letter “A,” and another letter “A,” and so forth until you get a raised letter “A.” That's three dimensions.
Now instead of it being ink, think of it being a droplet of saline or plasma or gel in which there are 10,000 cells. And instead of drawing an “A,” you make a line, and then you make another line, and then you make another line. And then you go a millimeter to the right, and you make some more lines. And now what you're doing is building two walls that can be connected eventually into a tube, but made of living cells, that will shake each other's hands, which is the miracle. We don't do it, they do it, they shake each other's hands and form the correct connections, and begin behaving as a larger biological construct.
That was the state of the art in 2007. And in the same way that it cost over $1 billion dollars to do a single genome in 2000 and now it's getting closer to like $100 to do a full genome, we’re at the same or even a faster rate of progress with the resolution we get printing tissues.
What technology in your portfolio sticks out as the most promising?
There’s a company called Turn.Bio that we helped found, that is out of Stanford. We have the patent for a method that reverts the age of individual cells to a youthful state and it's called epigenetic reprogramming. In the case of animal models, what it does is revert the healing capacity to a youthful functionality—it returns the strength to youthful functionality, the appearance to youthful functionality.
Notice I keep using the word “function.” Lots of folks talk about biomarkers, I don't care about biomarkers. I care about function. The difference is you could do a biopsy of your skin and the marker could say, well, this skin is the skin of a 50-year-old. But then you look at the person and they look 80. That’s function.
The potential of this technology is, if used in humans, to restore joints to a youthful state that would allow someone who might be headed toward a knee or a hip replacement, instead of proceeding to have a titanium ceramic hip replacement, you could actually just restore the youthful function of the joint. That was actually done in experimental mouse models.
Right now we are working on in vivo delivery solutions. It's probably still five years (at least) away, but if we can successfully deliver it in vivo—either intravenously, or in a pill—one could conceive of reversing a significant number of symptom, or the syndrome of aging, on the order of years. The nice thing about it is, if you have a muscle cell and you make it younger, it stays a muscle cell. Nobody wants to go all the way back to the Benjamin Button stage.
You’re saying it’s possible to make our bodies young again?
What I can say is that experimentally, we have good evidence that we can get there. Think of it as: it's 1903 and the Wright brothers just flew a motorized kite for 12 seconds. And 66 years later, we landed on the moon. Part of the reason our foundation, and others in our field, are covering a lot of geography is because the advances are self-amplifying—autocatalytic.
Today, when you get a transplant organ, you're getting a used part from someone who probably did not want to part with it, who has a history that is only imperfectly known, and the one thing you absolutely do know is it doesn't fit. It comes from a stranger usually and you'll be on drugs the rest of your life. Those are some things I would love to see end.
By growing an organ that's perfectly made for you, or made of you—meaning taking your own cells, cultivating them, regressing them to a youthful state, printing them to the perfect size and interior construction—all of our organs are unique to us. So you could do a high-resolution MRI or functional MRI and recapitulate/reproduce the actual interior structure, and have the printer print that. Put it in a bioreactor, make sure everything is all well hooked up, and then when you plug it in, all of the hookup points are where they ought to be for you.
Imagine if you're a surgeon, and you've got a part like that, instead of the used parts that you have to make fit?
What is the incentive for investors to get involved with longevity research?
More and more professional investors are getting involved for a number of reasons. One reason is there is a lot of investment money available, seeking returns. Another is that Google, Amazon, Facebook, Twitter, and Apple have pretty much hegemonically dominated the available space for innovation in the IT world.
There's not much more to be made in the IT space because that opportunity space has been thoroughly explored and exploited. Let's take the example of Amazon. Say somebody comes up with a good idea and puts their product on Amazon. The product does very, very well. Amazon looks at it and says, “hey, we could sell that for half price,” and they just do it. So why would anyone invest in doing something that they know Amazon's going to appropriate?
And that kind of thinking is going to gradually reduce the innovation rate within the IT tech world. And when innovation begins to decline, returns on capital decline. Investable capital will seek other homes. One of those homes will be us, and that’s proving to be true. We're starting to get very large professional investors interested in our companies.
The last great frontier of unsolved opportunity is in this new space called “longevity.” If you could cure Alzheimer's, that's potentially a trillion-dollar economic inflection point. Right now, many of these diseases are bankrupting nations, bankrupting the world, and it's just going to get worse. So aside from the fact that there are fortunes to be made, which is interesting to me but not why I'm doing this—I'm in charge of the nonprofit, I'm not allowed to become rich—at some point, some country is going to get the idea that we can't afford all these old people. That it's time to encourage them to move off this mortal coil, as a point of responsibility to leave.
I think it's a good idea to provide our race with options—an option that is of value to the individual, to the society, to the family, to civilization. It’s not a positive civilization that tells people they need to die because they cost too much. There are realities, so let's change reality.
If you could imagine a future 100 years from now, what might that look like?
We can't see over the horizon and the horizon appears to be between the years 2035 to 2040. What's happening along the way is that thousand-year-old institutions are collapsing. Hundred-year-old institutions are imploding. We're in a period where, in about 10 to 15 years, it will be impossible to predict what will happen. You cannot use linear prediction methodologies anymore because too many things are happening simultaneously and the feedback loops are impossible for my cranium to manage.
We went through this once, at least, from about 1870 to 1920, and ended up in the First World War. The world that existed before World War I simply turned off, it ceased to exist. And something entirely different arose out of World War I that I don't know who could have predicted. One of the most amazing facts of history is that every time government protocol in either Russia or the United States explicitly stated someone was supposed to launch the nukes, individual humans chose not to. So then the question is, how long are we going to be lucky before we get smart?
It feels to me that it will be less and less possible to be half glassful/half glass empty. We're getting to the point where it's either going to be full or empty. I'm not going to have much choice.
You’re saying we could live long healthy lives or we could nuke the whole world and be starting from scratch?
The fallacy of being a futurist is not recognizing that things don't work linearly all the time.
What I can say is that the body is a finely tuned, beautiful machine and it can be repaired, that's an article of faith on my part. It's above my paygrade to say what else is going to happen. What I can say is that we're in a period of crisis, and the things that are most important in humanity are disappearing, and that is goodwill, trust, and loyalty. These things are beginning to become scarce.
In the absence of those things, what holds civilization together? My answer is that nothing scientific will do that. Humans have to decide that they want to be decent because it's the right thing to do. Humans have to decide to be good because it's just good. And they have to wrestle and fight and learn how to deal with the fact that good is hard—just the definition is hard—still, it's something to aspire to, as opposed to ignore. What I can do is do the very best I can to fix that which seems to be fixable, along with others who wish to do the same thing.
Somebody once asked me “let's, let's say the impossible happens and you succeed in extending the healthy human lifespan—what would you do next?” And the answer is I've got this garden outside. What I would love to have is a homeostatic, isometric, self-managing greenhouse that looks into my iris and my retina, takes a blood sample and looks at my breath, checks my toilet assay, and grows the stuff I need for me. And the next thing you know, NASA asks me if I'll run their Deep Space Food Challenge. So I guess somebody was listening.
I hope this interview inspired your art as it did mine. Thank you so much for reading!
Until next week,
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