The Methuselah Prize

A startling new project was unveiled last Tuesday in the San Francisco Bay area. No, not Apple’s iPhone 6 or its watch, but the Palo Alto Longevity Prize. Never heard of it? Well, you still have a few more months to sign up to enter the competition to win $1 million for unlocking the secret to immortality. Is this just hype or is there some hope here for an important scientific breakthrough?

The basic idea is this: what we are doing now, attacking the maladies of old age one at a time, is simply trading off one bad disease for another. We’re already succeeding: the death rate from cardiovascular disease has fallen over the past several decades—and the death rate from Alzheimer’s disease has risen. As long as human life expectancy remains stable, we’re talking about a zero sum game in which you fix one problem and substitute another. So far, it looks as though dementia will be the big winner, which makes research aimed at turning off the switch that triggers all the diseases of old age very appealing. The underlying assumption of longevity research is that the degenerative diseases such as cancer, heart failure, and dementia are the result of the aging process. Preventing all the conditions that both limit life’s duration and impair its quality seems far more attractive than the disease-specific approach. But is it feasible and is it ethical?

The majority of credible scientists believe that life-extension is a very hard problem whose solution is not around the corner. The Palo Alto Longevity Prize, to the credit of its mastermind at Palo Alto Investors, Yoon Jun, is focused on somewhat more modest and potentially achievable goals. Part one of the prize is $500,000, to be awarded in June, 2016. It will go to a team that can restore the adaptive capacity of a laboratory animal; specifically, an aging animal will need to regain the heart rate variability characteristic of its youth. Part two of the prize is another $500,000 award, to be granted a year later to a team that increases an animal’s longevity by 50%. In both cases, the scientists will have to achieve their goal by enabling the animal to preserve homeostasis—the ability to maintain the status quo (temperature, blood pressure, etc) in the face of a stimulus, a capacity that is gradually lost with aging. Is this a worthwhile goal?

Impaired capacity for homeostasis is at the heart of frailty. The reason people lose their balance and fall easily, or get pneumonia when they contract the flu, or become confused when they are hospitalized is that they are vulnerable to modest “stresses.” So the key to physical frailty, and quite possibly to cognitive frailty (dementia) as well, is maintaining homeostasis. The Longevity Prize seeks to figure out how to do just that, but it is not without risks. As the Struldbrugs of Gulliver’s Travels showed, immortality without eternal youth is tantamount to hell-on-earth: failing vision, declining hearing, impaired cognition with no escape through death. Suppose unlocking the key to immortality does indeed prevent cancer and heart disease—but not arthritis and visual loss? The idea is to prevent all the degenerative conditions of old age, but suppose there isn’t just one switch, but several?

Even if we had confidence that achieving a longer life would not create a race of Struldbrugs, is it a good idea to devote scarce resources to trying to find the key to immortality? As NIH funding shrinks and the need to prioritize research questions grows, surely there are more urgent medical questions than how to live longer. Most people would opt to prevent premature death (infant mortality, teen suicide, cancer deaths in middle age) before they seek life-extension past the biblical allotment of three score and ten. Most physicians who witness the numerous ways patients suffer throughout life’s trajectory would recommend focusing on quality of life before quantity. And many people worry that if researchers did come up with an elixir of life, it would be so expensive that only a very small number of people could afford it, creating a new elite of Immortals.  So perhaps government should not fund longevity research, but what about the private sector? Google invested in Calico, a biotech startup devoted to finding ways to reverse aging. Earlier this month, Calico opened a new research facility in San Francisco where many talented scientists will search for the elusive spigot that can turn off the aging process. People in a free society choose to do all kinds of surprising things: they go bungee jumping, they sign up to travel to Mars, they smoke cigarettes. If Google wants to invest some of its advertising revenue on preventing the degenerative conditions associated with aging, why not?

If it’s reasonable to work on longevity, is offering a prize the right way to go? This approach got quite a bit of media attention a few years ago when Netflix promised $1 million to an individual or team that could improve its predictions of the movie ratings of individual viewers by 10%. This challenge stimulated a great many computer science graduate students and faculty members to spend hours trying to solve the problem. I know because my oldest son was one of them and he wrote about the math underlying the Netflix challenge for the on-line science journal, Science 2.0 when, after 3 years, a winner was announced. It turned out to be a good strategy for Netflix: for a relatively modest investment, the company recruited many fine minds to work on what would prove to be a difficult problem, without having to pay benefits or to pin their hopes for a solution entirely on one individual. Other organizations have issued similar challenges: the Millennium Prize, for example, announced by the Clay Mathematics Institute in 2000, offers $1 million for the solution to each of 7 great unsolved mathematics problems. As of today, only one of the 7 has been solved (and the individual to whom it was awarded, the reclusive and quirky Russian mathematician Grigori Perelman, declined the prize).

Perhaps the earliest use of a financial incentive to solve a scientific problem was the “Longitude Prize,” offered by the British Parliament in 1714 for an answer to how sailors could correctly establish their position at sea. Sailors had long used the stars to determine their latitude, but until the clockmaker John Hunter got his 20,000 pounds (worth about $5 million today) for solving the longitude challenge in 1765, they had been unable to determine their longitude. In recognition of the success of the first Longitude Prize—it was probably the last great breakthrough in navigation before Global Positioning Systems—a public private partnership in England recently launched the Longitude Prize 2014. This competition took an old approach and added a new wrinkle. A panel of experts came up with a list of 6 scientific problems in desperate need of a solution, and then asked the British public to vote on which one to sponsor. The election was held in June and the winner was the problem of antibiotic resistance: designing an easy to use, cost-effective way to test for antibiotic sensitivity at the point of care (which in turn would prevent doctors from giving a drug to which the relevant germ would not respond, an all too common scenario that both fails to cure the patient and also promotes further antibiotic resistance). The winner will receive 10 million pounds (about $16 million). Whether the competition will achieve its objective remains to be seen.  In many such competitions, including the Millennium Prize discussed above, nobody ever wins.

In sum, I doubt very much that the Longevity Prize will result in immortality and I’m glad that it’s a hedge fund and not the NIH that is sponsoring the competition. That said, it’s entirely possible that there will be valuable spinoffs from the kind of research that the prize is fostering, much as 19^th century anti-aging experiments using animal gland extracts led to hormone replacement therapy and tissue transplantation was stimulated by early 20^th century experiments in rejuvenation through grafting.