Vital Signs #141: Project Defy Death

Within a few months, Thiel had written checks to Kenyon and de Grey to accelerate their work. Since then he has doled out millions to other researchers with what he calls “breakout” ideas that defy conventional wisdom.

“If you think you can only do very little and be very incremental, then you’ll work only on very incremental things. It’s self-fulfilling,” Thiel, who is 47 and estimated to be worth $2.2 billion, said in an interview. “It’s those who have an optimism about what can be done that will shape the future.”

He and the tech titans who founded Google, Facebook, eBay, Napster and Netscape are using their billions to rewrite the nation’s science agenda and transform biomedical research. Their objective is to use the tools of technology — the chips, software programs, algorithms and big data they used in creating an information revolution — to understand and upgrade what they consider to be the most complicated piece of machinery in existence: the human body.

The entrepreneurs are driven by a certitude that rebuilding, regenerating and reprogramming patients’ organs, limbs, cells and DNA will enable people to live longer and better. The work they are funding includes hunting for the secrets of living organisms with insanely long lives, engineering microscopic nanobots that can fix your body from the inside out, figuring out how to reprogram the DNA you were born with, and exploring ways to digitize your brain based on the theory that your mind could live long after your body expires.

“I believe that evolution is a true account of nature,” as Thiel put it. “But I think we should try to escape it or transcend it in our society.”

During the first stage of their careers, the technologists spent their time solving problems in an industry that might seem glamorous but that in the grand scheme of things has been built on automating mundane tasks: how to pay for a book online, stream a TV episode onto a phone and keep tabs on friends. In contrast, they describe their biomedical research ventures in heroic terms reminiscent of science-fiction plots, where the protagonist saves humanity from destruction through technological wizardry.

Their confidence in that wizardry and their own ideas may lead them to underestimate the downsides and even dangers of the work they are funding, say some science philosophers, historians and economists. Their research in stem cells, neuroscience, genetically modified organisms and viruses, for example, tinkers with nature in big ways that easily could go awry — and operates in a largely unregulated space.

Their work to slow or stop aging, if successful, is also likely to lead to broader societal upheaval, increasing pressure on natural resources and on the economy, as people live longer, work longer and imperil already strained entitlements such as Social Security. Life extension also would radically change the most important building block of society: the family. No one seems able to predict what life might be like when half a dozen or more generations are alive simultaneously.

Laurie Zoloth, a bioethicist at Northwestern University, worries that some of the billionaires’ obsession with longevity may be driven as much by hubris as a desire to do public good.

“It’s incredibly exciting and wonderful to be part of a species that dreams in a big way,” she said. “But I also want to be part of a species that takes care of the poor and the dying, and I’m worried that our attention is being drawn away to a glittery future world that is fantasy and not the world we live in.”

Many of the younger philanthropists cite Bill Gates’ approach to giving as an inspiration. But while Gates has focused his foundation on saving those at the very early stages of life through his funding of child and maternal health initiatives, predominantly in developing countries, many of those in the new generation are focusing on the opposite end of the human life cycle in developed nations.

Gates has been very vocal in his praise of the generosity of Silicon Valley’s newly minted billionaires, but in January he expressed misgivings about their priorities. In a question-and-answer session on the Reddit online platform, he wrote, “It seems pretty egocentric while we still have malaria and TB for rich people to fund things so they can live longer.”

Hospitals and research centers have long been preferred beneficiaries of philanthropists. But instead of just writing checks to existing institutions, many of the technologists are pioneering new approaches for how the work should be done and how to measure success.

What many of the recent efforts have in common is a belief that computerized analysis of big data sets can deliver cures, predict outbreaks and discover patterns that would have been impossible for the human brain to process. An oft-cited example is Google’s flu heat map, which is built on the idea that an improved predictor for flu activity might be clusters of searches for, say, Tamiflu or “flu symptoms,” collected from Internet service provider addresses.

That approach turns the traditional scientific method on its head. In the United States, most biomedical research happens at a gradual and sometimes painfully deliberate pace. Scientists start with a hypothesis, conduct experiments to test it and then spend years refining and analyzing the results they collect. Their conclusions typically are not published until they have been corroborated by other scientists in the rigorous process of peer review.

The new medical and health-care research mines and maps the huge sets of digital fingerprints stored when people search, swipe, text, interact on social networks, shop, visit with doctors and leave geographic traces of their daily movements. Super computers  run through trillions of possible hypotheses at once and pinpoint patterns and correlations that may suggest solutions for some of the world’s most vexing medical problems. That approach already has led to some understanding of the role of thousands of genes in the human body — although scientists are not quite sure how to use most of that information for any practical medical purpose.

Google’s Sergey Brin, 41, has proposed a new kind of science that starts with masses of DNA and a community of people with certain genes. Brin has a mutation of the LRRK2 gene that is associated with a higher risk of Parkinson’s disease, and has said he thinks the new approach, could be “transformational.” He has donated $150 million to the effort.

“It’s not just money but more about driving awareness” among those with the same genetic subtype, said Brin’s estranged wife, Anne Wojcicki, who founded her own personalized genetics start-up, 23andMe. “No one cares if you just say there is this gene out there. But when you can bring together a community of people who are aware of their status...then suddenly you are engaged.”

Several of the Silicon Valley billionaires married women with backgrounds in science or medicine, and those wives direct the philanthropy.

Wojcicki, who studied biology and previously worked as a health-care consultant, is co-head of the couple’s foundation. Priscilla Chan, a pediatric resident at the University of California at San Francisco, with her husband, Facebook’s Mark Zuckerberg, 30, donated $75 million to San Francisco General Hospital, where 70 percent of the patients are underinsured or uninsured. The two couples also teamed up with others to create the Breakthrough Prizes for scientists who make discoveries that extend human life. Its $3 million payouts — given to six scientists each year — dwarf similar awards, including the Nobel Prizes, currently about $925,000.

Pam Omidyar, a biologist and former research assistant in an immunology lab, co-founded the Omidyar Network with her husband, eBay’s Pierre Omidyar, who became a billionaire at 31. They have donated millions to research about resiliency — the traits that help people bounce back from illness or other adversity.

And Page, who is now 41 and chief executive of Google, has made the biggest bet on longevity yet, founding Calico, short for California Life Company, a secretive anti-aging research center, with an investment of up to $750 million from Google.

Laura Arrillaga-Andreessen, who teaches a class on strategic giving at Stanford University and is the wife Internet pioneer Marc Andreessen, daughter of real estate magnate John Arrillaga and a well-known philanthropist herself, said that when many tech entrepreneurs look at the health-care system they see the “data of billions of people,” collected through blood tests, online profiles, food purchases and fitness trackers.

“When that data can be accessed and mined and utilized for good in an instantaneous manner,” she said, “that would be shattering in a positive way for the system as we know it.”

America remains deeply ambivalent about using new medical treatments to live radically longer lives. In a 2013 survey conducted by the Pew Research Center, 51 percent said they believed treatments to slow, stop or reverse aging would have a negative impact on society.

Two-thirds said they worry that radical life extension would strain natural resources, that only wealthy people would get access to new treatments and that “medical scientists would offer the treatment before they fully understood how it affects people’s health.”

Fifty-eight percent said treatments that would allow people to live decades longer would be “fundamentally unnatural.”

Political theorist Francis Fukuyama, a senior fellow at Stanford and former member of the President’s Council on Bioethics, argues that a large increase in human life spans would take away people’s motivation for the adaptation necessary for survival. In that kind of world, social change comes to a standstill, he said; aging dictators could stay in power for centuries.

“I think that research into life extension is going to end up being a big social disaster,” Fukuyama said in an interview. “Extending the average human life span is a great example of something that is individually desirably by almost everyone but collectively not a good thing. For evolutionary reasons, there is a good reason why we die when we do.”

Leon Kass, a physician and ethicist, poses a philosophical question: “Could life be serious or meaningful without the limit of mortality?”

Although many scientists say they are grateful for the entrepreneurs’ money and attention, some have been dismayed by what they see as Silicon Valley’s superiority complex and  insistence that the current methods used to fight disease are outdated and ineffective. At a medical conference in August 2012, for instance, Vinod Khosla, one of Silicon Valley’s most revered venture capitalists, likened the practice of medicine to witchcraft. He argued that machines are better than the average doctor and that disruption in health care was more likely to be driven by those outside the industry than those in the profession.

The reaction from the medical community was swift. Columbia University-educated physician Bijan Salehizadeh tweeted that he was “getting nauseated” from “the anti-doctor rantings of the silicon valley tech crowd.”

Some scientists also say they are concerned that private money — which can include seven-figure research grants and salaries that are two or three times what is offered in academia — distorts research priorities.

Preston Estep, director of gerontology for Harvard Medical School’s Personal Genome Project,  says some of the philanthropists are doing more harm than good by funding what he calls “pseudoscience” — approaches based more on emotional appeal than solid research. Of some of the work that is being funded by the tech crowd, he said, “nobody takes it seriously.”

“They are smart guys,” Estep said. “But they are not scientists.”

Since 2010, the National Institutes of Health’s budget has been cut by about $3.6 billion — or 11 percent — after adjusting for inflation, leaving thousands of research projects unfunded or underfunded. During the same period, private capital for scientific endeavors has surged. Venture funding for the life sciences hit $8.6 billion last year, according to PricewaterhouseCoopers and the National Venture Capital Association. And scientists are increasingly turning to crowdfunding sites such as Kickstarter to get their projects off the ground.

Prevailing theory among the tech entrepreneurs holds that the federal government is too risk-averse to properly drive medical research.  A failed project in Washington is akin to a great tragedy — with managers being called to testify at congressional hearings and Government Accountability Office investigations being launched into why so much taxpayer money was wasted. But in the entrepreneurial world, say tech leaders, failure is regarded as a learning opportunity on the way to the next innovation.

NIH director Francis Collins acknowledges the government’s financial constraints — he’s been lobbying for years for more funding — but disputes the notion that the biomedical research system is broken.

While he recognizes that what the entrepreneurs are doing is “amazing,” he said in an interview that their work is limited and a supplement to, rather than a substitute for , what the NIH, National Science Foundation, Defense Department and other agencies are pushing forward.

“They can’t pull together all the investigators of the country and the world to work on a problem together,” Collins said. “It’s not the international collaborative effort that the federal government can manage to assemble.”

The tech elite also have embraced as gospel two traditional scientific papers, both critical of the state of medical research.  The first, published in the Journal of the American Medical Association in 2005, is by John Ioannidis, a Stanford professor who has become the world’s foremost expert on the biases inherent to biomedical research. He argued that scientists, motivated by the pressures to publish and entangled in a web of conflicts of interest, manipulate data so often that it’s impossible to trust the body of scientific literature that  assesses the efficacy of hormone-replacement therapy or vitamin E or low-dose aspirin. Of 45 well-accepted journal articles about medical interventions, Ioannidis found, 14, or 31 percent, were later shown to be wrong or exaggerated.

The second, published last year and co-written by Harold Varmus, a Nobel Prize winner  and former director of both  the National Institutes of Health  and the National Cancer Institute, carried an alarming title: “Rescuing U.S. biomedical research from its systemic flaws.” In the opinion piece in the Proceedings of the National Academy of Sciences, Varmus and the other authors argue that much of the problem comes down to money. In essence, there are too many PhDs chasing too little money.

The entrepreneurs’ efforts are driven by the idea that they  have plenty of money, and they can do better.

Born in Germany and raised in Northern California, many of Thiel’s views on the future grew out of the science-fiction books and TV shows he loved while growing up. Thiel cites Arthur C. Clarke’s “The City and the Stars,” the author’s first novel, published in 1956, as being particularly influential. Set 1 billion years into the future, it imagines life in a technologically advanced city full of people who live forever by being stored in a computer and downloaded over and over again into new bodies.

“I prefer the original ‘Battlestar Galactica,’ the original ‘Star Trek,’ ” Thiel said. He doesn’t like the dystopian turn that science fiction has taken in recent decades.”

He is disappointed that the technological civilization predicted in the 1970s and ’80s has not yet materialized, but he is inherently optimistic that we can get there. “Where did we go wrong, and can we somehow get back on track?” he asked.

Thiel’s disdain for the status quo is clear in the manifesto for Breakout Labs, the grant-making group he set up through his foundation. It laments that scientists with bold ideas have been left out in the cold and promises to change that. “We want to jailbreak them from existing research institutions and set them free,” it says. In an interview, Thiel said the problem with the grant-making processes at NIH, the National Science Foundation and other major funders of research is that they are “consensus-oriented.”

For Thiel, death is the “great enemy” of humankind.

He said that in the past 25 years the pace of innovation in the biomedical realm has been demoralizing. “Nixon declared war on cancer in 1971, and there has been frustratingly slow progress,” he said. “One third of people age 85 and older have Alzheimer’s or dementia, and we’re not even motivated to start a war on Alzheimer’s. At the end of the day, we need to do more.”

Thiel’s philanthropic investments in aging grew out of a series of late-night conversations with a friend, author Sonia Arrison. Her book “100 Plus,” a national bestseller, lays out a future where living longer is the new norm.

For them, the possibility of a long life — perhaps to 150, nearly doubling the current average U.S. life expectancy — was exciting. Staying up late at night, the two would muse about ideas such as whether it was possible to bioengineer immune cells to recognize and kill cancer, or whether we could one day 3-D print human skin for burn victims — all sorts of different strategies to “repair people,” as Arrison put it.

In the future they talked about, everyone would be like Harriette Thompson, the 91-year-old who broke records this year after completing a marathon in 7 hours and 7 minutes.

They wondered: Would you have a longer childhood? Would you be able to have longer careers? Have six or more living generations of a family at once?

“Peter really has a love of life. He’s an explorer, a philosopher,” Arrison said. “I think people like that want more healthy life so they can experience more of it.”

It was Arrison who introduced Thiel to the scientists at the dinner-salon a decade ago. Since then, Thiel has funded such projects as a high-speed cooling technology for human organs so they could be preserved indefinitely and a way to grow bones using stem cells to replace broken ones.

“I’ve always had this really strong sense that death was a terrible, terrible thing,” he said. “I think that’s somewhat unusual. Most people end up compartmentalizing and they are in some weird mode of denial and acceptance about death, but they both have the result of making you very passive. I prefer to fight it.”

De Grey, who used the contributions from Thiel to start the SENS Research Foundation, a Mountain View, Calif.-based institute that conducts research on aging in its own labs and funds grants for academics, is focusing on cellular and molecular damage that accumulates throughout a person’s life.

“Think of a machine with moving parts,” he explained. “We’re trying to change what the body can tolerate.”

Kenyon, a longtime University of California at San Francisco professor who recently joined Calico, the Google-funded health venture start-up that aims to “cure” death, now is focused on the idea that “there seem to be life-extending processes that exist in nature, and they can be coaxed out of animals,” she said.

“They are just naturally present in some species that live long,” she said. Kenyon explained that organisms have mechanisms that are “almost like a surveillance system for terrorism.”

“You use a lot of mechanisms to search for anomalies in the environment,” she said. “If an animal sees a threat, it responds. . . . What’s really cool about this is that the mechanisms that protect it from danger can also protect it from the ravages of time itself. What if you could fool an animal into thinking there is a threat when there really isn't?” she said.

For all the thought Thiel has given to how to combat aging, he says he does not have a lot of specific ideas about what he would do if he could live significantly longer.

Instead of living each day as his last, he says, he lives it like he’ll live forever.

“If you did this, you might start working on some great projects you might otherwise not have attempted because you didn’t think you’d finish,” Thiel said. “You’d treat strangers a lot better because you’d likely see them again. You’d be a much better steward of the Earth than if you thought it was your last day and you were having a crazy party or something.”