Among Calico’s first hires was Cynthia Kenyon, now its vice president of aging research, who 20 years ago showed that altering a single DNA letter in a laboratory roundworm made it live six weeks instead of three.
Google’s founders created an academic-biotech hybrid they call an R and D company to follow up on such clues, providing nearly unlimited funding to a group of top researchers. Calico has hired stars like artificial-intelligence specialist Daphne Koller. With equal contributions from Google’s parent company, Alphabet, and the drug company AbbVie, it has $1.5 billion in the bank
Calico is an elite university research group housed within a corporate bunker, doing mostly basic science. It has more than 100 employees and has assembled a Noah’s ark of yeast, worms, and more exotic creatures like the naked mole rats, which are kept at the Buck Institute for Research on Aging, about 30 miles from Calico’s South San Francisco headquarters.
What’s different about a mole rat (which lives ten times longer than mice and most other rodents) ? That is the sort of costly, open-ended question Calico can afford to ask. And then there’s the seven-year study Calico is financing that will follow 1,000 mice from birth to death to search for biomarkers of aging. Right now, there’s no proven test for a person’s “biological” age; finding one would be scientifically useful and possibly lucrative. “They don’t open the kimono much,” says Brian Kennedy, a Buck Institute scientist who interacts with Calico. “I think they believe we need a broader grasp on the biology of aging. They recognize it can’t possibly be simple.”
Scientists don’t know enough about why animals age. Calico’s Hal Barron, hired from Roche to lead its drug development efforts, told the National Academy of Medicine in 2015 that there would be no short-term payoff. “We believe you have to take a very long view,” he said, “and not rush into the clinic until you really know what you are doing.”
A hundred and seventy five years ago most people died from infections, not from old age. Thanks to vaccines, better nutrition, and all-around improvements in public health and medicine, life expectancy at birth in wealthy nations has doubled from 40 to around 80 years, an average gain of 2.5 years per decade. But now that we live longer, we have traded up to a new set of killers that are harder to beat: cancer, heart disease, stroke, and dementia.
For all these diseases, aging is the single biggest risk factor. An 80-year-old is 40 times as likely to die from cancer as someone middle-aged. The risk for Alzheimer’s rises by 600 times. But what if it were possible to postpone all these deaths by treating aging itself?
“I think we have failed in our effort to attack chronic disease when we attack them one by one,” Sierra says. “And the reason is that they have one major risk factor, which is the biology of aging.”
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.
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, Jeff Bezos joined investors who 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.
Other scientists say it is time to begin large human studies of “geroprotectors”—drugs that could decelerate aging altogether. One such effort is being spearheaded by gerontologists at Albert Einstein College of Medicine, in New York. The medication they hope to test, metformin, is used to treat diabetes. It cropped up as an anti-aging prospect after scientists reviewing medical records found that people taking it not only were much less likely to die than other diabetics but died at a 15 percent lower rate than all other patients.
Metformin lowers blood sugar levels, one clue it may have something in common with a low-calorie diet. But getting a study off the ground hasn’t been easy. To convince the U.S. Food and Drug Administration to approve the trial, doctors decided to measure metformin’s effectiveness in preventing three separate diseases: heart attack, dementia, and cancer. “They do not recognize aging as a disease, so what we have done is choose diseases of aging with minimal overlap in their causes,” says Steven Austad, a biologist at the University of Alabama at Birmingham and scientific director of the American Federation for Aging Research, which has endorsed the metformin study. “If it simultaneously delays them, that would indicate a slowed rate of aging.”