Writing

FREETHINK

This piece was originally published on Freethink.

Biggest science prize ever aims to
extend human healthspan by a decade

The largest ever XPRIZE aims to find out how
medicine can engineer radically healthier lives.

By Raiany Romanni, November 29, 2023.


 

Do humans have a biological or moral obligation to die young? Of course, “young” is subjective. Greenland sharks often live to be centuries old in good health. Until the 1900s, the human life expectancy was 31, including deaths at birth and a plethora of infectious diseases throughout life. Today, it’s 74 — and some calculate it’s increasing by 3 months for every year one stays alive. Yet the average healthspan — the number of years we live in good health — hasn’t fully kept up with the recent increase in average years lived.

Americans typically record a 12-year gap between healthspan and life expectancy, and the costs of this healthspan gap are disheartening. Today, some 40 million people in the United States — predominantly women — are unpaid caretakers of millions of older adults in declining health. By 2029, America will spend $3 trillion dollars yearly (half its federal budget) on adults aged 65 or older. Developing countries like Brazil, where the population of adults aged over 65 will triple by 2050, are getting old before getting rich.

For all our progress, we have made only decent headway in extending the human healthspan in the absence of disease. Compared to our progress in transcending nature through, say, heavier-than-air flight, our aging profile remains somewhat archaic. The negative effects of aging (think how some 90% of all COVID deaths happened to adults over 60) start to show up at nearly the same age today as they did in 300 BC. This is the case, in good part, because aging itself has never been the target of medicine. Not until now.

A new science prize, the largest one in history with a purse of $101 million, is setting out to change the way we understand healthy aging. The XPRIZE Healthspan, launched this week and designed to be awarded by 2030, will incentivize science teams globally to develop safe, effective, and affordable interventions to close the healthspan gap. The competition will build on significant advancements in the field to improve cognitive, immune, and muscle function, with the ultimate aim of adding at least 10 years to the healthspan of persons aged 65 to 80.

Awards will be given out for improvements in function relative to age-related declines expected over 10 years ($61 million), 15 years ($71 million), or 20 years ($81 million), with an additional $20 million in milestone awards. And as a side effect, these scientific advancements focused on health extension may make us all live longer, too.

The prize, which I helped design as a bioethics consultant, has the mission to create a future where healthy aging is possible for everyone. It also gives an entirely new meaning to the notion that we, as a species, may have a moral obligation to die young. But is improving the way humans age even possible? And will these interventions be accessible for all?




The ethics of buying health

Some bioethicists have quipped (rather seriously) that they — and reasonable humans — should like to die sometime around the age of 75. The feeling isn’t foreign to some 56% of Americans, who say they would not support treatments that slow down aging. The argument goes like this: A decade or so after we retire, we become burdens to our families, to ourselves, and to our governments. Therefore, life becomes a net-negative. And so we might as well go gently into our good night. Proverbially staying up until 1, 2, 3 AM — or pulling an all-nighter — is selfish. It’s not a choice without costs for other agents in a zero-sum world, the theory goes.

A common misconception is that with improved aging, governments would spend more on older adults, but in fact medical and social costs would be lower. With sprightlier limbs and younger brains, older adults may continue to innovate well into their golden years, and the average age for the award of Nobel Prizes might shift, say, from 55 to 65.

Other bioethicists take no issue, in principle, with the idea of improving how we age. Haven’t we unnaturally extended our life expectancy already? Cholera and COVID-19 aren’t morally desirable just because they are natural. But — this group insists — we must draw the line if there’s a possibility that healthy life might be distributed inequitably. Or if age-improving therapeutics might exacerbate power imbalances, allowing older adults to keep their positions of power at the expense of younger generations. 

Even Elon Musk (not a bioethicist) has said, in an interview with Tim Urban, that engineering humans to have a better aging profile — like that, say, of bowhead whales, who live to be 100 largely without the negative effects of human aging —  is more of a moral battle than a technical one. “Aging can obviously be fixed,” Elon claimed in a recent post on X. “The real question is whether it should be.” He doesn’t know the answer, and so leans towards no.

I helped design the XPRIZE Healthspan because I trust there has to be a more solutionist approach to this problem than either a) do nothing, or b) do nothing

Indeed, this same attitude might have prevented us from developing vaccines, germ theory, or dialysis; and those who wish to forgo “extraordinary medical measures” (a legal term) must appreciate that most medical measures were at some point extraordinary. Most inventions were also, at first, inaccessible to most. Even kings in the 19th century often died from today’s minor infections. Medicine has a long history of once-expensive and frightening interventions — like heart transplants and IVF — which now help save, create, and improve billions of lives. 

XPRIZEs have historically tackled efforts for which commercial incentives are lacking (see the second largest XPRIZE for carbon removal, funded by Elon), and this is no exception. It’s often more profitable, for instance, for pharmaceutical companies to develop treatments that lengthen the unhealthy life of a sick patient by a few months than to develop mechanisms which improve overall health. The plan is for this global competition to align the development of health-extending therapeutics to market incentives, so that aging science becomes viable — and investable.

With a total addressable market of everybody and pressing government incentives to close the healthspan gap, this XPRIZE and other efforts in the field may build a future where age-improving therapeutics become mainstream medicine, dwarfing the revenues and impact from today’s weight-loss drugs. 

XPRIZE founder Peter Diamandis tells me “the goal is to democratize these therapeutics, and technology is a force that turns scarcity into abundance.” The Hevolution Foundation is the largest sponsor for the prize, and is committed, as CEO Mehmood Khan shares, “to advancing geroscience and reshaping the approach to aging.” 

People who believe aging should not be improved because this crosses a natural, divinely conceived line; or because of the possibility of inequitable distribution; or because this might rob us of innovative thinking or of limited resources (I answer the latter points in two previous articles) often haven’t spent enough time considering the problem.

We do not halt Alzheimer’s research, for example, out of fear that not all humans on Earth will immediately afford dementia drugs; or that we might end up with non-demented autocrats. While ever-healthy dictators make for a good Hollywood story, 99.9% of people in the real world struggle, instead, with the more humdrum pains of paying rising health bills from age-related diagnoses; suffering from age-related poverty; or from the psychological stresses of watching one’s loved ones gradually lose their personality, dignity, and function. 

As prize sponsor Chip Wilson — founder of Lululemon — shares, “​it does not make any sense to have a long lifespan without being healthy.” Yes, a long list of technical problems will need to be solved to enable a future where the increase in human wisdom doesn’t correlate linearly with disheartening diagnoses. (See this report detailing the field’s main bottlenecks.) And yes, the first age-improving therapeutics may not be immediately accessible to all. They may take years to reach a favorable risk-benefit profile — and even then, they will have side effects. 

This is because the subject at hand is the translation of science into medicine — not magic. Medicine is clumsy. It exists in a world filled with pain, trade-offs, and injustices. And it’s still worth pursuing — just as the “extraordinary” measures that kept some lucky or wealthy people alive in the 20th century have been refined and scaled to now improve billions of lives. 

I believe humans have a moral obligation to die young. But if science can make us die young at the ripe age of 100, all the better — for ourselves, for our descendents, and for our planet



 

BOSTON GLOBE

This piece was originally published in The Boston Globe Ideas section.

 

Want to live to 150? The world needs more humans.

Believe it or not, we have an underpopulation problem to solve

— and there’s good reason to believe aging isn’t inevitable.


By Raiany Romanni, March 29, 2023.



Perhaps no idea was more influential on 20th century history than Thomas Malthus’s hypothesis that uncontrolled population growth would lead to famine, war, and an overall lack of resources. In the 1910s, Boston was home to the “brain trust” of the movement for state-led eugenics, which later caused much suffering in Europe. In 1912, when Harvard’s president emeritus called for the “forced sterilization” of the “feeble-minded,” he encountered no backlash from the progressive elites of his time. In 1980, China crystalized Malthusian theory into history when it implemented its now-infamous one-child policy.

Malthus’s 1798 “Essay on The Principle of Population” was wrong for many reasons, not least of which was the racism embedded in his belief that “the lower classes” would take up zero-sum resources. He also erred in his devout view, as an ordained minister, that “hunger and disease were implemented by God to stop populations from exploding.” But above all, the very notion of overpopulation proposed by Malthus has been overturned. Increased access to education, voluntary birth control, and female economic empowerment have instead paved the way for an emerging underpopulation crisis.

In 2020, Massachusetts joined the list of 25 American states recording more deaths than births. In the same year, only two countries in the Organization for Economic Co-Operation and Development had a fertility rate of at least 2.1 children born per woman — which is needed to maintain population replacement.

Malthus was right in one sense: The size of a population is a huge factor in its economy. But he failed to anticipate that we might come to lack healthy adults to come up with and fund solutions for humanity’s most pressing crises. He did not foresee — and many people still do not appreciate — that one 21st-century farmer, engineer, or baker can produce far more resources than she consumes in her lifetime. Just like Paul Ehrlich, who wrote in the bestselling 1968 book “The Population Bomb” that “the mother of the year should be a sterilized woman with two adopted children,” Malthus was gravely off base.

Last year, the global population crossed 8 billion. In recent decades, it has also enjoyed the highest levels of nourishment, housing conditions, comfort in travel, and education in all of history, as Steven Pinker documents in “Enlightenment Now.” The 20th century’s scientific breakthroughs gave us vaccines, chemotherapies, and antibiotics. In just one century, average life expectancy rose from 31 to 68.

But this extraordinary leap in life expectancy happened without a corresponding increase in health-span. Because aging itself hasn’t been considered a medical disorder, people today generally spend half their lifetime in declining health.

Some 90 percent of all deaths in developed countries are due to to age-related decline, including cancers, heart disease, dementias, and severe infection. By 2029, the United States will spend an unprecedented half of its annual federal budget — $3 trillion, or thrice its military outlay — on adults 65 or older, on measures like Alzheimer’s care and retirement pensions. By 2050, Japan will lose some 20 million people, while Brazil’s senior population is set to triple. About 50 million Americans — predominantly women — are now unpaid caretakers of older adults, at a $500-billion-a-year opportunity cost.

Could new technologies solve these problems by extending the healthy years of long-lived populations? This is the question the emerging field of aging research has set out to answer — and labs in some of Boston’s elite institutions are among those with data suggesting that aging can be not just slowed down, but also reversed.

If we solve aging, we may well solve our emerging underpopulation crisis.

And we have, I will suggest, an ethical imperative to do both — even though tackling aging itself as a medical problem remains a contrarian idea.


The project of the 21st century

Two centuries after Malthus remarked that “we should court the return of the plague” and “reprobate remedies for ravaging diseases,” a growing number of scientists, investors, and bioethicists believe we can and should engineer longer and healthier lives.

In his 2019 bookLifespan,” Harvard geneticist David Sinclair wrote that “aging may be more easily treatable than cancer.” After several years working to understand and control the biological mechanisms of aging, he tells me, his lab is showing that aging may be “like scratches on a CD that can be polished off.” His team’s latest findings were published in the journal Cell on Jan. 12. Their paper suggested mammalian aging is in part the result of a reversible loss of epigenetic information: our cells’ ability to turn genes on or off at the right time.

In “Lifespan,” Sinclair points out that if we cloned a 65-year-old person, the clone wouldn’t be born old — which says a lot about how our “youthful digital information” remains intact, even if this 65-year-old’s genetic expression and cell regulation mechanisms are presently functioning less than optimally. There seems to be, as Sinclair notes, a backup information copy within each of us, which remains retrievable.

There is no guarantee that cellular reprogramming will work in humans — but after decades of (at times, highly criticized) work, Sinclair’s lab published what is set to become a widely influential study on the role of epigenetic change in aging. Futurist Peter Diamandis, trained as a physician and now executive chairman of the XPrize Foundation (a science and technology nonprofit for which I consult), tells me aging must be “either a software or a hardware problem — solvable by a species capable of developing vaccines for a novel virus within months.”

Indeed, the human life expectancy of 80 years and the current health span of roughly 40 (when most chronic illnesses begin to appear) are not just economically alarming — they don’t appear to be a biological imperative.

Humans are one of only five species in the animal kingdom that undergo menopause. Lobsters are often more fertile at 100 than at 30. Naked mole rats’ chances of dying do not increase with age. Bowhead whales live to 200 and are incredibly resistant to the diseases of aging.

Other examples abound — and the genetic therapies that could translate these features into human bodies are becoming increasingly precise. Promising research in human genes, cells, and blood drives home that aging is a malleable process that can be decoupled from the passing of time.

It is well established that aging can be sped up, slowed down, and reversed. This is done every day with diet, mental health practices, and exercise. What’s novel about this century’s science is the promise to engineer therapies that might control the aging process more effectively.

By conservative estimates, robust aging therapies could free up half the American federal budget every year, making it possible for more older adults to remain in the workforce. These therapies could effectively prevent nearly all cancers, dementias, and heart diseases, and even avert fiascos of communicable diseases like the COVID pandemic, in which age is the major risk factor for severe disease. (COVID-19 will cost the global economy $12.5 trillion by 2024.) Low-income and other vulnerable populations stand to gain the most, because they suffer the most when diagnosed with age-related diseases.

Yet despite the enormous promise of aging therapies, the field hasn’t attracted a correspondingly large amount of government funding. Out of the $4 billion devoted to the National Institute of Aging yearly, only $300 million goes to fundamental aging research.

Why?

It cannot be because aging research lacks scientific results. Research into Alzheimer’s disease may have fewer credible results than the far younger field of aging — yet it enjoys many times more funding. If an idea is sufficiently compelling to a civilization (like the reversal of climate change is becoming to ours), then replicable scientific results can be the goal of the research, not the prerequisite for undertaking it.

For too long, aging research was incompatible with Western culture. It was only in 1906 that Alzheimer’s was recognized as a disease, and only around the 1920s that the public narrative of cancers shifted from their being godsends (with which to interfere would be hubristic) to intervenable disorders. Aging was thought to be a feature designed by evolution to furnish human lives with meaning.

Yet natural selection only rarely optimizes for human happiness. Evolution favors the flourishing of genes, not organisms. And as several evolutionary biologists have remarked, our genes live on when we reproduce — making our bodies evolutionarily superfluous.

It follows that aging therapies would be no less natural than cancer therapies or vaccines designed to tackle any other pandemic in which older adults are the most vulnerable. And, as Harvard geneticist George Church tells me, “there is no reason why aging therapies should cost more than the recent COVID vaccines — as little as $2 per dose.”


The tiny industry of aging therapies

Aging research is woefully underfunded, understudied, and understaffed. For every aging lab, there are thousands of cancer labs globally — even though 96 percent of cancers happen to adults aged 35 or older.

Democratic governments declare wars on the diseases of aging (though not on aging itself) because a full 100 percent of the population is onboard. By comparison, only 38 percent of Americans believe aging should be slowed down or reversed, according to the Pew Research Center. As a result, a mere 0.5 percent of the National Institutes of Health budget is devoted to fundamental aging research.

In its best years, research on the biology of aging receives $3 billion in private funding — or less than half the market size of bug spray.

The problem with leaving our aging crisis for venture capitalists to try to solve is twofold. First, the priorities of the private sector are not to protect vulnerable populations or decrease human suffering. Venture capital often doesn’t care about the grief of watching one’s parents die; the agony of becoming an unpaid caretaker to a loved one; or of losing one’s cognitive abilities, bit by bit — unless alleviating any of this suffering can be monetized within 10 years of investment. Second, without governmental funding on the scale of what was mustered for COVID vaccines, the private sector is unlikely to deliver safe and effective aging therapies very soon.

Despite non-trivial advancements in the science, the private funding flowing into longevity isn’t enough to attract the world-class talent warranted by a goal like age reversal. In the past, small and underfunded teams have produced astonishing breakthroughs in science — and with advancements in AI, this will increasingly be the case. But for a goal like age reversal — just as for the reversal of climate change — a shift in public narrative may be imperative.

Waiting until global warming has been reversed to then convince the voting public of the merits and urgency of climate science would be an ill-timed strategy — just as waiting for better results in aging science to then decide this socioeconomic crisis should be solved may be unsound.

The average voting person’s disapproval of aging research in the West may soon cause non-democratic governments to lead the charge in this made-in-America idea. Saudi Arabia has the one government openly devoted to age reversal, with a $1 billion annual fund. Alex Zhavoronkov, CEO of Insilico Medicine, a longevity-oriented drug-discovery company that has raised over $415 million, tells me he moved the company’s R&D to China to capitalize on “half a trillion dollars’ worth of infrastructure and hundreds of thousands of scientists [provided by the government] to enable AI-designed drugs.”

Ultimately, Americans struggle to accept aging research because we fear its moral implications. If we engineer ourselves out of aging and live unprecedentedly long, healthy, and abundant lives, would we risk engineering ourselves, too, out of meaning?

With longer lives, we would have to guard against a kind of reverse ageism. Older adults may retain undue power, stifling opportunities for younger people. This does not obviate our ethical imperative to achieve a more humane health system.

If we lived longer, would there be more traffic or higher carbon dioxide levels? In the short term, yes. In the long term, however, more minds translate into better solutions. A planet with 10 billion people is likely to have greater housing and nourishment needs. But it is also far likelier to have electric self-driving cars, high-density and digitally optimized mass timber buildings, interplanetary settlements (for which we will need aging drugs), and hyper-productive vertical farming.

In the end, no technology is ever fully good. Surveys show that the American public believes that for aging therapies to be morally sound, they must be “safe, effective, affordable, available to all, and cause no side effects.” But that’s self-deceiving. Costly and only occasionally safe or effective cancer therapies are a case in point. As a rule, solutions create unintended problems, for which new solutions must be devised. The answer isn’t to stop funding scientific progress, but to refine it until clinical therapies achieve a favorable risk-benefit profile.

When I ask George Church about these ideas, he looks at me with the resoluteness of a seasoned scientist — but in his eyes I see a childlike, nonconformist spark. “Age reversal can be done,” he tells me. “And it will be more humane than anything that happens in nature, if we do it right.”

Raiany Romanni, a philosopher and bioethicist in Boston, is working on a book about the ethics of age-reversing technologies.


Washington post

Technology promises

to change the meaning of death

New research shows that we might be able to revive bodies we once thought beyond repair. That could increase medical inequities, but it’s still worth pursuing.


By Raiany Romanni, August 19th, 2022



When artificial kidneys were first used as a medical tool in 1945, it became unnervingly clear that human organs, until then essential to the human makeup, were replaceable. Soon after, hearts — once thought to be the linchpin of humanity — were quickly substituted by external devices, supplanting the inexplicable complexity of human muscle with far simpler, synthetic parts.

This month, a team of Yale scientists partially revived the cellular function of pigs a full hour after the animals’ brain and cardiac waves had flatlined. With the help of their OrganEx system, they restored some cellular activity in the pigs’ hearts, livers and — most meaningfully to bioethical discussions — brains. Though the pigs did not regain consciousness, the Yale researchers demonstrated that vital organs may remain treatable for longer than most scientists have suspected. While this finding doesn’t yet have clinical applications, it may soon offer a new challenge to medical claims about where life ends and death begins.

The brain is the last human organ whose parts cannot be replaced synthetically: As philosopher Daniel Dennett writes, brain transplants are the one kind of operation where one should wish to be on the donating side. If at one point our hearts epitomized the singularity of humans, today the gooey, floating mass within our skulls delineates what we understand as human life.

Until the middle of the 20th century, a patient could be pronounced dead without debate if her heart stopped and her lungs ceased to function. But new ventilators and defibrillators meant that checking for rising, falling or fluttering chests was no longer a valid way to diagnose death. In the late 1960s, physicians who were concerned about the viability of transplantable organs proposed a new metric for thinking about our mortality, one focused on brain death rather than on the functioning of other organs. Their approach soon took hold, and when today’s physicians record their patients’ time of death, they mean the moment when medical devices can no longer register or restore consciousness.

As Harvard bioethicist Robert Truog suggests, what we formally calldeath” consists “more of a moral judgment than a biological fact.” In other words, brain death is less the point at which an organism is definitively gone and more an arbitrary limit, designed to permit legal and medical systems to move on. Though there are no properly documented cases of recovered consciousness after a correct brain death diagnosis, Truog predicts that medical advances may at some point preclude us from using the term “brain death” as a legally binding elision with what the U.S. President’s Council on Bioethics defines as “human death”: the irreversible cessation of the “fundamental work of a living organism.”

With the successful revival of some brain and cardiac cellular activity in mammals, the day when medical technologies will again force us to update our definition of human death looms slightly closer.

This promise is at once thrilling and terrifying. If we extrapolate on the potential of the Yale team’s OrganEx system, we may eventually be capable of reviving silent brains and restarting organs that once would have been considered irreversibly dead. (As it turns out, “irreversibly dead” is not a pleonasm.) In just a few decades, we may be forced to acknowledge that death isn’t a biological absolute so much as an administrative process. Death certificates might indicate that the deceased’s family couldn’t afford to reboot their loved one — or to preserve their body long enough to let such technologies take hold. With advancements in cryonics and emerging technologies such as OrganEx, this is no longer just a science fiction hypothetical but a reality conceivable within our century.

The distinction between life and death, in other words, might become a more painful sort of moral judgment: a matter of who can afford to keep a body functioning. In such a future, health inequities would be exacerbated; the wealthy could repeatedly forestall their death, while those least well-off would be forced to accept an indeed “irreversible cessation” of their bodily functions. The fact, however, is that this future shouldn’t sound unfamiliar to those least well-off today. In 2022, a person dies almost every hour while waiting for an organ transplant. Patients of color are especially vulnerable to such deaths, having fewer systemic chances to delay their fate.

The notion that death could be, and sometimes is, an administrative hurdle — the result of missing ventilators, organs or, in the future, superior but expensive OrganEx devices — makes funerals difficult to swallow. We might ask whether we should continue to develop life-extending technologies if they risk exacerbating our already horrifying inequities.

The answer, I suggest, is yes. In the 1940s, the vast majority of patients with failing kidneys did not have access to dialysis — though some exceptionally well-off, well-connected or simply lucky ones did. Since then, millions of low-income patients have been saved because we accepted this period of inaccessibility. In 2022, artificial kidneys are far from equitably distributed, with those who lack health insurance often unable to afford them. Yet the only way of increasing access to cutting-edge medical interventions is by encouraging more funding for them — even if this temporarily worsens disparities.

If the philosopher William MacAskill is right — and if we do our part to ensure we have a future to look forward to — humanity is only entering its adolescence and has a moral obligation to improve the lives of future generations. In fact, with the current pace of technological advancement, it is not implausible that these futuristic, life-extending medical technologies may become available for low-income people alive today. And one might argue that the fastest, most ethically permissible way of lowering the price of extraordinary medical therapies is by having the wealthy subsidize them as initial customers, as philosopher John Rawls implies.

DNA sequencing is a case in point: The first incomplete sequence cost $2.7 billion in 2003 and offered no clinical relevance. In 2011, Steve Jobs paid $100,000 to learn his genome sequence and his tumors’ genes, without encouraging results. Today, thanks at least in part to Harvard geneticist George Church, who advocated for the democratization of genome sequencing since the 1990s, it is the upper-middle-class American’s $299 go-to Christmas present and is only beginning to provide clinical benefits. Tomorrow, insurance companies and European governments may offer DNA sequencing free of charge, allowing vulnerable populations to benefit from this once-luxurious tool.

The practice of forestalling death is as old as it is undivorceable from the concept of medicine. As history shows, today’s extraordinary measures will simply be tomorrow’s measures, saving the lives of real humans, both rich and poor. This will remain true even when we again tweak our definition of where life ends and death begins.


 
 
 

“There is hardly a belief more harmful than that biological decay is a mystical, kind, or dialectical force, guiding humanity towards its predetermined and unalterable telos.

It is human agency—with the sweat, faults, and capriciousness of the living—that engenders progress. It is our own ever-ungainly understanding of terms like “disease” and “health” that designs the future of our species.”

 
 
 

“Progress happens not one funeral, but one healthy, living human at a time. It is not up to the allegorical workings of death, but to each living human to advance our ethics, our politics and our technologies.

Progress is the result of the hard work and actions of innovative, living thinkers — like Vitalik Buterin, who co-founded the decentralized blockchain Ethereum at 23 years old, and like Henry Ford, who created the Model T (the world’s first affordable car) at 45.”

 

ABC

“But, if in the Middle Ages the gods were thought to punish human sin with, for example, the Black Plague, today we think of poor health in old age as the set-in-scripture decay of the body — a testament to human frailty in the face of a vast and callous universe, the denial of which would result in the sin of arrogance.

We think of aging as the product of this orphic thing called “time”, ignoring that species far less resourceful than ours live on for centuries longer, and some (like the American lobster) do not decrease in strength, do not have their metabolism slowed down, and become more rather than less fertile, with the passage of time.”