Episode #4

degrey

Exceptional Extension of Human Lifespan--A Morning with Aubrey de Grey, PhD.

Written by Travis Christofferson

This Episode centers on Aubrey de Grey. An article is posted to accompany the interview explaining Dr. de Grey's mission---that focuses on achieving exceptional human longevity. If you aren't familiar with Dr. de Grey, read the article first. As Dr. de Grey will explain, with the explosion in biotechnology, and incredibly powerful tools now at researchers disposal, it's not nearly as far off as most think.

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greyarticpicBy all account Aubrey de Grey lives an interesting life. On the surface, his schedule looks perhaps more like a rock star than a scientist; replete with heavy travel—straddling anywhere from Silicon Valley to the Moscow Institute of Physics and Technology--- hotels, late nights in pubs, spirited debates, an open polyamorous lifestyle, and a full media docket; from 60 minutes to the New York Times. But cutting through the center of his globetrotting, free-wheeling existence is a deep and urgent sense of mission. De Grey’s raison d'être is this: he says he simply wants to keep you healthy. As benevolent and ordinary as that sounds, digging a little deeper reveals a meticulously drawn out plan that goes far beyond just keeping us healthy in the traditional sense: De Grey wants to keep you in your 25 year-old body in-perpetuity.

 

And why not? Hidden within that question is where we find the miracle in the man---de Grey is the right combination of saucy fearlessness and bold visionary to believe he can, and should, reengineer a glitch in Darwin’s original plan—specifically, he wants to design a way out of nature’s post-reproductive apathy toward our bodies. And if given enough resources, de Grey says that his research foundation; Strategy for Engineered Negligible Senescence (SENS) can usher in an audacious era of post-Darwinian evolution---where we determine our own destiny; releasing ourselves from the whimsical, and apathetic forces of natural selection. If SENS is successful, for all practical purposes, its plan will enable us all to stay youthful to our heart’s desire---granting us access to a post-modern version of Ponce de Leon’s fabled fountain. But even for the brazen Brit it is an admittedly lofty goal rife with political, sociological, and ethical consequences, but one according to de Grey, is an inevitability, and is much closer than most may think.

Born in London in 1963, the 53 year old, who never knew his father, was pushed by his artist mother to learn science and math as a young boy. After studying computer science at Cambridge, de Grey began an entrepreneurial venture to write artificial intelligence software. But de Grey’s career was marked to take a sharp turn one night in Cambridge upon meeting a University of San Diego Geneticist on sabbatical named Adelaide Carpenter. Both were at a party thrown by a grad student when Carpenter recalls de Grey cornered her and demanded that she “justify her existence.” Carpenter says she was immediately taken by the uninhibited and handsome young man in front of her. After a few more pints, some late night dancing, the two woke up in the same bed and have been together ever since. As de Grey’s career in computer science begin to stumble he was already well into a transition. With Carpenter as his tutor, de Grey had been learning about genetics and gerontology in his spare time. What began as a mild interest, at some point morphed into a passionate, self-funded mission to deeply understand the forces of nature that imperceptibly a, minute by minute, transform the vitality of youth into the unmistakable frailty of the elderly.

De Grey’s unorthodox educational arc to uncloak the invisible forces of aging—hopping from conference to conference while voraciously consuming journal articles in the space between—landed him with an astonishing mastery of the subject. Over the course of a couple months he wrote a book clarifying the floundering mitochondrial theory of aging, filling in some critical chasms that plagued the 60 year old theory. The effort earned him a doctorate from Cambridge and overnight thrust de Grey into a serious role within the field of gerontology. But de Grey was not satisfied.

June 25, 2000: It came to him all at once in a sleep deprived haze. After an inter-continental flight from Cambridge to California, followed by a day of spirited debate at an invitation-only conference, de Grey lie awake at 4 AM in his Manhattan Beach hotel room, his mind a swirling turbine of frustration. In between brief moments of fitful sleep a vague notion began to form edges. So much focus was on trying to understand metabolism in order to prevent the corrosive damage of aging, but what if we focused on the damage itself. This single change in strategy, what de Grey calls his “Eureka Moment”, was the incandescent clarity he needed to take the next step.

As it has been unraveled, human metabolism has presented itself as a vastly interwoven network of biblical complexity. In all its subtle perturbations and branching pathways de Grey was not alone in wondering if it was even fully understandable. The overwhelming majority of the anti-aging effort centered on trying to tweak metabolic pathways hoping to slow the damage of aging---a strategy that, because it attempts to blunt the cause of aging, has strong intuitive appeal to most gerontologists. But de Grey realized this strategy would only, could only, go so far. The damage caused by normal metabolism was deeply anchored—it was a side-effect of being alive---it could never be completely controlled without killing the object. And truth be told, the attempt, for the most part, was largely meaningless. The difference between the healthiest country (Japan) and the 14th (United States) in terms of longevity is only 4 years. The only consistently proven way to extend lifespan was caloric restriction. And the most bang-for-the-buck from caloric restriction occurred in short-lived species like mice---a lifetime of denial for humans probably would only net a few more years---hardly worth it.

But inside the exhilarating moments of his hotel-room epiphany de Grey realized he could completely side-step the staggering complexity of human metabolism and the meager results of caloric restriction type interventions. The whole concept, de Grey reasoned, was comparable to everyday experience---like maintaining a house. Rather than try to stop the inevitable forces of sun, wind, and rain that degrade a structure overtime, just repair the damage as it occurs and the structure can stand forever. The change in strategy, de Grey realized, was a paradigm shift. The frustration born from trying to parse the complex forces of aging was, in a single stroke, swept away by redefining the problem. This changes everything, he thought.

Invigorated, de Grey shot out of bed and began pacing in his hotel room while stroking his prodigious beard. He began to create a mental list of the types of damage that accumulate with age. He whittled it down to seven: 1. Chromosomal mutations. 2. Glycation: the warping of proteins by glucose. 3. The accumulation of extracellular junk: like beta-amyloid. 4. The accumulation of intracellular junk: like lipofuscin—or age spots. 5. Cellular senescence: cells stuck in a sort of suspended animation while releasing toxins. 6. Depletion of stem cell pools. 7. Mitochondrial mutations.

As he continued to pace it dawned on de Grey that various degrees of promising research were well underway for “fixes” to the seven forms of damage. The seemly impossible dream to drastically prolong human health was within reach.

With the path before him laid out, and to put additional thrust behind the research to repair the damage of aging, de Grey and David Gobel founded the Methuselah Foundation in 2003, and later spun off the SENS foundation in March of 2009. The mission stated on the website: “Our goal is to help build the industry that will cure the diseases of aging.”

De Greys 2007 book, Ending Aging, lays out the plan to counter each of the seven forms of damage. Indeed they are not subtle; but instead are an unapologetic, wholesale attempt to reengineer the human body. For example, to combat the consistent mitochondrial DNA mutations that occur as a side effect of normal metabolic free radical generation (something that antioxidants will never be able to do) de Grey proposes putting extra copies of mitochondrial DNA within the nucleus where it would be protected—a process called allotropic expression that has already shown itself to be possible.

Another example of the SENS strategy consists of an upgrade to our cellular waste management system. Intracellular gunk inevitably accumulates with age (think age spots). In looking for a solution de Grey noticed nature had already done the work, and his solution would simply borrow nature’s intellectual property. The idea is no different than most forms of bioremediation in use today that employ bacteria to clean up a mess. Bacteria have evolved enzymes to degrade almost every substance on the planet. SENS solution is a cellular form of bioremediation: by placing copies of the necessary bacterial enzymes within the cellular recycling bins known as lysosomes our cells should remain pristine as far as the eye can see.

SENS strategy to keep us healthy, in addition to piquing the imagination, often stirs up fiery controversy. Perhaps it was the grandiose way the media portrayed the idea early on ---as a science fiction dream of sorts. Phrases like “The Profit of Immortality” irked some seasoned gerontologists who viewed de Grey as the new kid on the block, and his bold proclamations as misguided and wildly unrealistic. “Aubrey will say something that’s the biological equivalent of 'Let’s build a 1,000-story building on the head of a pin, and I’m like, 'Wait, wait, let’s go back to that first part again,'” Judith Campisi, a top cell biologist at Lawrence Berkeley National Laboratory, said in a Popular Science article about de Grey. But as difficult as de Greys “fixes” seem, Campisi added, “I wouldn’t waste my time talking to him if I thought it would never happen.”

Yet, despite their criticism, you’d be hard pressed to find, at the top level, a gerontologist that doesn’t at least respect de Grey and take his view with varying degrees of seriousness. In fact, some of the most respected think he is spot on. Including the greatly respected Bruce Ames, who attached his name on a 2002 paper outlining the logic of SENS titled: Time to Talk SENS: Critiquing the Immutability of Human Aging

Somewhat surprisingly, the mission of SENS’s has even been a tough sell to the general public. At the 2014 St. Gallen Symposium, a global gathering of “Leaders of Today and Tomorrow” that takes place annually in May at the University of St. Gallen, Switzerland, veteran journalist Stephen Sackur of the BBC interviewed de Grey on stage in front of a packed audience. Ten minutes into the conversation Sackur asked the audience a question: “Instinctively how many of you think drastic life extension is a good idea?” Only a scattered few raised their hands. Sacker then reversed the question: “Who thinks that it is a very bad idea, not just for ourselves but for society as a whole?” The vast majority then raised their hands.

Over the years de Grey has learned to refine his message. Now he cringes when the media uses the word immortally in articles. Such a message colors the mission of SENS as fanciful or unrealistic. Today, de Grey counters that he works on immortality with the claim he works on prolonging health. Much more than a play on semantics to reframe the narrative, it also represents what would be a seismic shift in public health strategy. De Grey is quick to point out in TED talks, speaking invitations, and interviews that hundreds of diseases are not really distinct in and of themselves. Diseases like Alzheimer’s, Parkinson’s, and cardiovascular disease, rather than individual diseases, are better classified as side effects of being alive--in other words, all are consequences of aging. And the distinction matters. Even if good treatments for Alzheimer’s are developed, for example, you’ve gotten nowhere because you haven’t stopped the underlying cause, which is aging. If successful, the treatments SENS is working on, will, in one fell swoop, cure hundreds of diseases at once. “Extreme longevity will just be a side effect of the process”, says de Grey.

After BBC journalist Sackur highlighted the general public’s gut-reaction to immortality with his audience poll, de Grey slightly twisted the question, conducting his own impromptu poll: “How many in the audience would like to get Alzheimer’s disease?” Nobody raised their hand. De Grey then raised the ante: “Hands up anybody who thinks there is some age that they would like to get Alzheimer’s disease?” Again, no hands went up. “I’m sure the response would be the same if I asked about cardiovascular disease or any other. Now the misconception is that you can think that you don’t want all these things but you do want aging. That’s not possible. They are all parts and parcel of ageing. You can’t have one without the other. Get over it.” The simple shift in frame; subtle change in perception; revealed a strangely flawed logic---the audience began a collective nervous laughter at the embarrassing realization; and then broke out in applause.

If de Grey’s impromptu poll hinted at a certain hypocrisy then statistics pull back the curtain on it entirely. For every person in the audience that raised their hand declaring they are opposed to increasing longevity; how many will take heroic measures to prolong their lives through traditional medical treatments like chemotherapy, replaced hips, stents, bi-pass surgery, and transplants right up to the end in a desperate attempt to eke out a precious few more moments of life?

The answer is: the vast majority. One out of every four Medicare dollars is spent on care near the end of life---to the tune of well over 100 billion dollars a year---often without any prolonging of life.

After a lengthy talk with de Grey I found it difficult to not appreciate the inherent logic of SENS mission. He certainly throws down an extremely persuasive argument --- stitched together with plenty of charisma, rational, and wit. As de Grey urges us to notice, all the diseases of aging flow from the same spigot---and we should focus on turning off the spigot rather than mopping up the endlessly forming puddles below. The enormously expensive end-of-life care, from the perspective of SENS, looks like a desperate and futile game of whack-a-mole. Yet, strangely, as a society, we seem to have an instinctual aversion to tinkering with our natural lifespan. To be sure, since the days of living in caves, humanities has, with various degrees, intervened on our natural lifespan in the purest sense. Anytime we get vaccinated, take antibiotics, or get an organ transplant, we are altering Darwin’s original plan. We seems ready, almost eager, to accept new and disruptive technologies ---artificial intelligence, driverless cars, nuclear fusion-- yet we have a visceral aversion to tinkering with the inexorable sine-wave of birth and death. It is understandable. Death is deeply embedded in our sense of humanity; our literature, our poetry—passing the baton to our children. It’s hard to completely wrap your arms around what it means. Our lives; an arc of incremental goals going up, reaching an apex, and then declining into the twilight, will flatten out into a perpetual present. To remove death is to extract an essential cog of our being. Yet de Grey says this is nothing more than nostalgia. To remove death from the human equation is to remove an enormous amount of suffering---plain and simple, claims de Grey.

At this point, how quickly it arrives is just a matter of money. SENS’ budget has been growing and has attracted the attention, and money, of billionaire PayPal founder Peter Thiel. "Almost every human being who has ever lived is dead. Solving this problem is the most natural, humane, and important thing we could possibly do,” says Theil. “You can accept it, you can deny it or you can fight it. I think our society is dominated by people who are into denial or acceptance, and I prefer to fight it.”

greybotpicAs you read this article, the mission of de Grey and SENS, because of groundbreaking new technologies, is drawing eerily close. With the recent development of CRISPR, and refined stem cell technologies, or a combination of the two, researchers say they are a year or two away from trials attempting to reverse aging in humans.

At some point in the not-too-distant future you may be given a choice---a modern twist to Shakespeare’s original query: To be or not to be, that is the question? And like the searching Prince Hamlet you will have to weigh the pain, burden and unfairness of life against the exhilarations, discovery, and meaning.

De Grey has his own answer to this question: “I don’t know about you, but I have a big backlog of stuff I still want to do.”