Editor's note: H&HN Daily published the first of this two-part series on Oct.28.
In April 2012, just weeks before her seventh birthday, Emily Whitehead was admitted to the Children's Hospital of Philadelphia after a second recurrence of the most common form of childhood leukemia, B-cell acute lymphoblastic leukemia, or ALL. Treatment of pediatric ALL is one of the great success stories of modern medicine: More than eight in 10 children who receive this terrifying diagnosis can now, in fact, expect to be cured completely, through a standard regimen of chemotherapy.
Emily was not among them. By the time she and her parents arrived at Children's Hospital, two rounds of chemo had proved futile. Hairless and wan, she was on the brink of organ failure. But an experimental therapy developed at the Children's Hospital-affiliated University of Pennsylvania School of Medicine by immunologist Carl June, M.D., had shown early promise in combating B-cell leukemias in several adult trial subjects. Although there were still many unknowns about the rigors and effectiveness of the treatment, and their daughter would be the first pediatric patient to receive it, Emily's parents grasped desperately at this straw.
Emily is back home now. She's a bouncy, vivacious fourth-grader with shoulder-length brown hair and no trace in her blood or bone marrow of the disease that only a few years earlier would have killed her. She's the sunny poster face for what Science magazine proclaimed the breakthrough of the year for 2013: cancer immunotherapy.
Immunotherapy is a revolutionary "personalized" medical technique by which blood is harvested from a patient; and the genetic machinery of its T cells — the body's potent main defense against most pathogens but normally unreactive to cancer cells — is altered by introducing an inactivated, genetically modified HIV virus. The souped-up blood is reinfused. The patient's own T cells now can detect signature proteins on the cancer cells and swarm to destroy them.
Several immunotherapeutic approaches like the chimeric antigen receptor therapy Emily received (known as CART or CTL019) are under active investigation for a variety of cancers. Results in initial trials have been highly encouraging — in some instances, astonishing. So much so that the Food and Drug Administration has designated CTL019 a "breakthrough therapy" meriting expedited review for clinical use.
Moreover, notes Stephen Minger, chief scientist in the cellular sciences division of GE Healthcare in the United Kingdom, major pharmaceutical companies and niche startups are "piling on this now." "Individualized cell therapy is at the inflection point," he maintains. "It's going to change fundamentally the way we treat cancer … [but it also holds promise for] orthopedic indications, repair of bone and cartilage … organogenesis … autoimmune diseases like multiple sclerosis, lupus, inflammatory bowel disease and Crohn's disease, where there's been very little therapy available and patients are sick all the time and in a lot of pain … .
"We're starting to see clinical benefits from targeted immune therapies that spare normal tissue and are completely curative," he summarizes. "It's not just a niche. We're looking at treating very large patient populations to whom we've had very little to offer before. Now we have to address how to deal with millions of them a year. There's a huge amount of excitement around this. We're all ecstatic. But the hard stuff is ahead of us. It's going to be totally, totally disruptive."
That's exactly what Aubrey de Grey puts stock in. The breathtaking advance ("out of nowhere," marvels Minger) that has given a dying 6-year-old the prospect of a long and healthy life (it's too soon to say that Emily is cured, but her doctors are optimistic; three-quarters of the first CART recipients remain cancer-free) could mean that her life will be very long indeed, suggests de Grey.
It could even, he reasons, extend to 1,000 years.
De Grey is an English computer scientist who married a biologist and over the dinner table became fascinated by the phenomenon of aging. He began studying the biochemistry of old age, earned a doctorate from Cambridge University, wrote the first of several books outlining scientific consensus on the cellular-level causes of aging and established (and later helped to fund through an inheritance) a nonprofit organization sponsoring research into what he styles "strategies for engineered negligible senescence," or SENS.
Based in Mountain View, Calif., the SENS Research Foundation — for which de Grey serves as chief science officer — is conducting and backing studies into technologies like immunotherapy that will enable people to get older without getting sicker or weaker.
SENS is focused not on extending life per se, de Grey emphasizes, but rather on preventing and periodically repairing the various kinds of accumulated damage — too many useless "senescent" cells interfering with normal metabolism, too few replacement cells, chromosomal and mitochondrial mutations, excessive cross-linking of "junk" proteins — that produce the diseases and infirmities we now consider natural concomitants of old age. They range from arthritis to cancer to cataracts to diabetes to heart disease to senile dementias to stroke. All, de Grey maintains, will become mere historical memories as scientific breakthroughs like cancer immunotherapy are applied sequentially in a preventive maintenance approach to human health.
"Rather than tackle the diseases of aging one at a time, and largely unsuccessfully," he tells audiences as he stumps for SENS, "we'll be able to attack them as a unified network of integrated processes. The human body is just a machine. Replacement of parts at the cellular and molecular level is a perfectly good way [to reverse the aging process]."
Such is de Grey's confidence in the imminence of "regenerative" and "rejuvenative" biotechnological fixes for the scourges of old age that he thinks someone now in healthy midlife — even as old as 60 — might plausibly look forward to living to 1,000. And that doesn't mean 900 of those years will be spent as a stooped, addled, hard-of-hearing, half-blind, medical-appliance-riddled graybeard — the prospect that makes most people queasy when they contemplate a 1,000-year lifespan. Rather, de Grey proposes, the old will remain young: vital, potent, engaged contributors to society enjoying a protracted — very protracted — prime of life.
Scoffers point to the downsides of such longevity. They worry about overpopulation, environmental impacts, lack of opportunity for the young, societal disruption, sheer boredom. De Grey has arguments to counter each of those objections. Mostly, though, he stresses that "we won't have 200-year-olds for another 100 years, or 1,000-year-olds for another 900 years, and quite a lot may have changed by then." Technological and cultural evolution will not suddenly stop as more people live longer. Just as we've adjusted to aviation and computers and living into our 80s, we'll engineer accommodations.
Meanwhile, he points out, "150,000 people die every day around the world, two-thirds from the diseases of old age. That's an incalculable amount of suffering!" To those who argue from religion that man should not "play God" by extending human life past ordained "natural" limits, de Grey responds that "every religion makes it clear we have a duty to alleviate and eliminate suffering. It would be a cardinal sin if we didn't work on this stuff."
Reaching Escape Velocity
So, what about the startling proposition that someone alive today — say Emily Whitehead — might live to blow out an additional 991 candles on a future birthday cake? Here, in an email, de Grey explains his reasoning:
"I think the various SENS interventions have at least a 50 percent chance of being implemented within 20–25 years from now, and that they will postpone people's age-related decline by at least 30 years.
"Because these are rejuvenation therapies, i.e., damage repair, they will work just as well on people who are already age 60 or so as on younger people: They will restore one's biological age to young adulthood.
"Therefore, they will very powerfully 'buy time.' People who are 60 when first treated will only be biologically 60 again when they are chronologically 90. They won't be as easy to 're-rejuvenate' then as they were the first time, because the imperfections in the therapies (which are the only reason the people got back to biologically 60 at all) will now dominate the damage in the people's bodies. But, in the meantime, there have been 30 years of research and development geared to closing those gaps, to reducing those imperfections. And 30 years is an awfully long time in technology, including biomedical technology. So, in fact, these 90-year-old 60-year-olds very probably will be in a position to be re-rejuvenated, with SENS 2.0 shall we say, such that they won't become biologically 60 for a third time until they are chronologically 150. And so on. This is what I've called 'longevity escape velocity.'
"Why 'very probably?' you may ask. Who's to say that the gaps will be closed rapidly enough? All we know is that over the history of SENS so far, we have not needed to revise [our] plan: New types of damage have been discovered, but they all fit cleanly into the existing categories, which means that they are all amenable to the same types of therapies, which means that those therapies are very likely to be capable of being adapted to the new type of damage rather quickly. The longer SENS stands the test of time, the stronger this argument becomes, and I'd say it was already very strong even a decade ago.
"What about the person being already 60? The thing here is that the benefits from SENS will depend on one's pre-existing biological age, not chronological. So, if the above numbers pan out, the first cohort who will mostly be able to avoid aging indefinitely are probably 30 or 40 now. But people who already live exceptionally long — e.g., to 110 — don't get there by staying alive in a grim state of health for decades: They do it by staying biologically youthful for a lot longer than the rest of us. So, the first person to avoid aging indefinitely could, indeed, be 60 today, because he or she will be maybe 85 when the therapies arrive, and will be one of those exceptional people, so he or she will be in the biological state typical of 60- or 65-year-olds and the therapies will be just as beneficial.
"Finally, that number 1,000. That comes from simple statistics. If you're a young adult in the developed world today, your chance of dying within the next year is less than one in 1,000. That means, if you could just stay that way as long as you live, then you'd have at least a 50 percent chance to live to 1,000. Today, throughout our adult life, our chance of dying in the coming year goes up by 10 percent per year — but that is what SENS is all about stopping."
To your health.
David Ollier Weber is a principal of The Kila Springs Group in Placerville, Calif., and a regular contributor to H&HN Daily.