Google founded the California Life Company, or Calico Labs, to work on aging, and has put a large amount of money into this project. It is all comparatively secretive, but so far the evidence suggests that this will, sadly, turn out much the same way as the Ellison Medical Foundation, which is to say (a) work on extending the map of all cellular biochemistry relevant to the progression of aging at the most detailed level coupled to (b) attempts to slightly slow aging via pharmaceuticals. The project is headed by someone who has little interest in translational research, the business of bringing therapies to market, and those involved - for the most part - are not people with a track record of paying attention to the SENS program of repairing damage to produce rejuvenation. The SENS research agenda is to my eyes the only viable way forward to produce meaningful extension of healthy life any time soon, and certainly the only way to help older people by turning back aging at later stages. It is also far closer to realization and far less expensive to develop than efforts to safely alter human metabolism to slow the rate at which damage is done. The field of aging research has all too little funding in comparison to its potential, but it doesn't suffer from a lack of fundamental research anywhere near as much as it suffers from a lack of taking what is already well known about the forms of cell and tissue damage that cause aging in order to build therapies here and now.
David Botstein is Calico's chief scientific officer. He is 74, with a grizzled shadow of beard reaching up from his collar. In November, I found him at a lecture hall at MIT, where he offered a rare window onto experiments under way at Calico. Botstein, a well-known Princeton geneticist whom Calico recruited out of near retirement, was in town to celebrate the birthday of a successful former student, now a sexagenarian. "The pleasure is coming to see old friends. The not-so-pleasure is if these guys are 60, what am I?" In his lecture, Botstein described several technologies - four, in fact - that Calico has for isolating old yeast cells from the daughter cells that bud off them. These old cells are tracked and subjected to a comprehensive analysis of which genes are turned up or turned down, a technique that is Botstein's specialty. Botstein told me Calico is exactly what Google intended: a Bell Labs working on fundamental questions, with the best people, the best technology, and the most money. "Instead of ideas chasing the money, they have given us a very handsome sum of money and want us to do something about the fact that we know so little about aging. It's a hard problem; it's an unmet need; it is exactly what Larry Page thinks it is. It's something to which no one is really in a position to pay enough attention, until maybe us."
Botstein says no one is going to live forever - that would be perpetual motion which defies the laws of thermodynamics. But he says Cynthia Kenyon's experiments on worms are a "perfectly good" example of the life span's malleability. So is the fact that rats fed near-starvation diets can live as much as 45 percent longer. The studies Botstein described in yeast cells concerned a fundamental trade-off that cells make. In good times, with lots of food, they grow fast. Under stresses like heat, starvation, or aging, they hunker down to survive, grow slowly, and often live longer than normal. "Shields down or shields up," as Botstein puts it. Such trade-offs are handled through biochemical pathways that respond to nutrients; one is called TOR, and another involves insulin. These pathways have already been well explored by other scientists, but Calico is revisiting them using the newest technology. "A lot of our effort is in trying to verify or falsify some of the theories," Botstein says, adding that he thinks much of the science on aging so far is best consumed "with a dose of sodium chloride." Some molecules touted as youth elixirs that can act through such pathways - like resveratrol, a compound in red wine - never lived up to their early hype.
According to Botstein, aging research is still seeking a truly big insight. Imagine, he says, doctors fighting infections without knowing what a virus is. Or think back to cancer research in the 1960s. There were plenty of theories then. But it was the discovery of oncogenes - specific genes able to turn cells cancerous-that provided scientists with their first real understanding of what causes tumors. "What we are looking for, I think above everything else, is to be able to contribute to a transformation like that. We'd like to find ways for people to have a longer and healthier life. But by how much, and how - well, I don't know." Botstein says a "best case" scenario is that Calico will have something profound to offer the world in 10 years. That time line explains why the company declines media interviews. "There will be nothing to say for a very long time, except for some incremental scientific things. That is the problem."
To some, Calico's heavy bet on basic biology is a wrong turn. The company is "my biggest disappointment right now," says Aubrey de Grey, an influential proponent of attempts to intervene in the aging process and chief science officer of the SENS Research Foundation, a charity an hour's drive from Calico that promotes rejuvenation technology. It is being driven, he complains, "by the assumption that we still do not understand aging well enough to have a chance to develop therapies." Indeed, some competitors are far more aggressive in pursuing interventions than Calico is. "They are very committed to these fundamental mechanisms, and bless them for doing that. But we are committed to putting drugs into the clinic and we might do it first," says Nathaniel David, president and cofounder of Unity Biotechnology. This year, investors put $127 million behind Unity, a startup in San Francisco that's developing drugs to zap older, "senescent" cells that have stopped dividing. These cells are suspected of releasing cocktails of unhelpful old-age signals, and by killing them, Unity's drugs could act to rejuvenate tissues. The company plans to start with a modestly ambitious test in arthritic knees. De Grey's SENS Foundation, for its part, has funded Oisin Biotechnologies, a startup aiming to rid bodies of senescent cells using gene therapy.