(Part 3 of a multiple part series from Perpetual Life, broken into segments for your convenience)
In 2013, Google launched Calico, short for the California Life Company, with a billion dollars in funding. “Calico added a tremendous amount of validation to aging research,” George Vlasuk, the head of a biotech startup called Navitor, told me. “They have money, brainpower, and time.” But Calico has proved to be extremely secretive. All that’s known is that it’s tracking a thousand mice from birth to death to try to determine “biomarkers” of aging—biochemical substances whose levels predict morbidity; that it has a colony of naked mole rats, which live for thirty years and are amazingly ugly; and that it has invested in drugs that may prove helpful with diabetes and Alzheimer’s. (The company declined to comment.) 11
A number of longevity scientists confess to disappointment with Calico’s direction. Nir Barzilai, a geneticist who is a leader in the aging field, told me, “The truth is, we don’t know what they’re doing, but whatever it is doesn’t really seem to be attacking the problem.” Another scientist who’s familiar with Calico’s workings said that it’s pursuing its mission judiciously, but that the company began, fatally, as a vanity project. The scientist said, “This is as self-serving as the Medici building, a Renaissance chapel in Italy, but with a little extra Silicon Valley narcissism thrown in. It’s based on the frustration of many successful rich people that life is too short: ‘We have all this money, but we only get to live a normal life span.’ ”
Maris, who has retired from Google Ventures, strongly disagreed with that view. “This is not about Silicon Valley billionaires living forever off the blood of young people,” he said. “It’s about a ‘Star Trek’ future where no one dies of preventable diseases, where life is fair.”
If Silicon Valley billionaires end up being sustained by young blood, they will satisfy an ancient yearning. In 1615, a German doctor suggested that “the hot and spirituous blood of a young man will pour into the old one as if it were from a fountain of youth.” In 1924, the physician and Bolshevik Alexander Bogdanov began young-blood transfusions, and a fellow-revolutionary wrote that he “seems to have become seven, no, ten years younger.” Then Bogdanov injected himself with blood from a student who had both malaria and tuberculosis, and died. Parabiosis, the surgical linkage of circulatory systems, has had a mostly grisly history in humans—when it was tried as a desperate measure on terminal cancer patients, in 1951, a two-year-old boy lost part of his foot to gangrene—and in rodents, which resisted being conjoined. A 1956 study warned, “If two rats are not adjusted to each other, one will chew the head of the other until it is destroyed.”
We kept trying. In 2005, a Stanford lab, run by a stem-cell biologist and neurologist named Tom Rando, announced that heterochronic parabiosis, or an exchange of blood between older and younger mice, rejuvenated the livers and muscles of the older ones. Vampires everywhere felt validated. Last fall, on “The Late Show,” Stephen Colbert warned teen-agers that President Trump would replace Obamacare with mandatory parabiosis: “He’s going to stick a straw in you like a Capri Sun.”
Entrepreneurs and venture capitalists also had their straws poised. Rando said, “I’ve had a lot of meetings with young billionaires in Silicon Valley, and they all, to varying degrees, want to know when the secrets are coming out, both so they can get in on the next big thing and so they can personally take advantage of them. I say, ‘This is not an app. If you come at biology from a tech point of view, you’re going to be disappointed, because the pace is much slower.’ ”
In recent years, the parabiosis field has grown quarrelsome. Is the rejuvenative key the presence of young-blood proteins, or the absence of something like SASP? Could it be a cellular by-product from one mouse, or the effect of borrowing a younger mouse’s liver? In 2014, the Harvard scientist Amy Wagers concluded that young-blood factors, particularly a protein called GDF11, gave older mice a stronger grip and renewed their brains. Most of her colleagues questioned her results, and the drug company Novartis promptly did a study that suggested the exact opposite: you should blockade GDF11. Wagers told me, “Different groups have reported that amounts of GDF11 go up, go down, or stay the same with age.” With a bleak laugh, she added, “Clearly, one group is right.”
After Rando’s colleague Tony Wyss-Coray showed that young blood can foster new neurons in the hippocampus region of the brains of old mice, a company called Alkahest spun out from his work. Alkahest has begun to sift the more than ten thousand proteins in plasma, in hopes that the right protein cocktail can cure Alzheimer’s—a process that is expected to continue for more than a quarter century.
When I visited Alkahest recently, Joe McCracken, the vice-president of business development, cued up side-by-side videos of genetically identical, equally aged mice. They were about to run a Barnes maze: a disk dotted with black circles, one of which was a hole—a laboratory version of a burrow in which to escape a diving hawk. During previous runs, they’d been trained to remember the hole’s location. McCracken, who was with two colleagues, explained that the first mouse had been treated only with a placebo of inert saline. We watched it nose here and there, uncertainly, before finally stumbling upon the hole. It took a minute and twenty seconds. The men clapped, releasing their anxiety. “It’s me in the parking lot, looking for my car,” Sam Jackson, the company’s chief medical officer, said. Then McCracken played the video of a mouse that had been tuned up with plasma from eighteen-year-old human beings. That mouse darted purposefully toward one sector of the maze, found the hole, and scooted into it in eighteen seconds. The execs grinned and shook their heads: youth.