Villeda, a stem cell researcher at the University of California San Francisco, was one of the first to collect data to suggest that’s not as crazy as it sounds.
Back in the 2000s, when Villeda was still a graduate student in biology at Stanford, he and his colleagues had reinvigorated a long-dormant field in regenerative medicine with a remarkable finding. When they stitched together the circulatory systems of young and old mice, they noticed that the blood that flowed from the young animals into the older animals seemed to reverse signs of aging.
Since then, other scientists at Stanford, Harvard, and UCSF have reached similar conclusions. In their studies, all involving mice, the technique, known as parabiosis — achieved either through directly connecting circulatory systems or through copious injections of blood plasma from a young animal to an older one — improved muscle function, cognition, and even the sense of smell in older animals. The opposite appears to be true, too: When young mice are given old blood, the signs of aging worsen.
It’s compelling and captivating work. And it’s no wonder a Silicon Valley venture capitalist with a known obsession with immortality has taken notice.
This week Inc. (and then Gawker) reported that a member of Thiel’s venture capital firm reached out to Ambrosia, a company that’s now running a clinical trial on humans (Villeda has no affiliation with Ambrosia). The trial is registered with the federal government, and it aims enroll 600 people over the age of 35 and inject them regularly with the blood plasma of people under the age of 25.
Jeff Bercovici, who wrote the Inc. piece, also spoke to Thiel about his interest in parabiosis in an interview in 2015. And he suggests there are others in Thiel’s community of magnates who may already be doing it.
“There are widespread rumors in Silicon Valley, where life-extension science is a popular obsession, that various wealthy individuals from the tech world have already begun practicing parabiosis, spending tens of thousands of dollars for the procedures and young-person-blood, and repeating the exercise several times a year,” Bercovici reported.
Villeda understands why people are excited to try parabiosis. Humans have always been captivated by the prospect of cheating death. “But we have a responsibility as scientists to tell people exactly where we are,” he says.
The early research is groundbreaking and exciting, he says. But the interest in parabiosis is already getting ahead of the research. He fears that the science will be maligned by a rush to market a “youth serum.” Or worse: A black market for young people’s blood will arise out of the hype.
“I’ve gotten so many emails and so many texts — emails from people I don’t know, who are getting hopeful and excited about these articles,” he says. “And that causes me pause.”
Here are a few of the reasons to be skeptical and proceed slowly.
Most of these studies were done in mice that were sewn together, not injected with blood
It’s only been in the past few years that scientists have injected mice with others’ blood. Most of the previous studies, upon which this work, is built physically connected the vasculature of a younger mouse with that of an older mouse for weeks at a time.
Think about that — and how it can’t be replicated in humans.
Meanwhile, there are other reasons the research in mice may not translate to humans.
A big one is dosing.
“In mice, we’ve gave them about about 5 percent of their volume of plasma for each injection, we gave them eight injections over a month, we’re doing it every three days,” Villeda says. “So that’s quite a lot quite frequently. We haven’t really extrapolated that into humans yet.”
We also can’t really compare mice ages with human ones.
In the mouse studies, typically, an 18-month-old mouse will get donations from three-month-old mice. How does that translate to human research? We have no idea.
No one knows why the blood is causing the positive changes
The big idea behind parabiosis is that there are factors in young blood — perhaps stem cells, hormones, or other proteins — that can cause genetic changes or structural changes in an older animals.
But “we’re barely now understanding what those [factors] are,” Villeda says.
Some work out of Harvard has identified a factor in young blood that aids skeletal muscle function. But more discoveries will need to be made to understand exactly how young blood can benefit older people. “We don’t know if there’s one factor,” Villeda says. “We all think there’s many factors.”
In science, it’s not enough for an intervention to be shown to work in a preliminary trial. Scientists have to know how it works to best avoid side effects and unintended consequences.
More work on understanding the mechanism may even make blood transfusions irrelevant to this research. If scientists can identify the factors, they can possibly isolate and manufacture them for further testing.
No one knows if injecting yourself regularly with a young person’s blood is risky
This is big. While no mice have shown to be negatively impacted by the transfusions, there’s still uncertainty about what the side effects might be.
“So far in everything that we’ve done, in all these different labs, we don’t see anything [negative],” Villeda says. “However things that have been brought up … what if we overstimulate cells that are proliferating? Can that promote things like cancer? We don’t have any evidence for this, but it is a possibility that will need to make sure it’s not.”
Unfortunately, the Ambrosia trial may not help us answer these questions
The Ambrosia trial will test for “100 biomarkers that may vary with age,” Science reports. But as Villeda notes, the field isn’t in agreement over what biomarkers do actually correlate with aging. So the results may be hard to interpret.
“Everyone jumps to, ‘Are we going to live longer?’” Villeda says. “And we don’t have any evidence for that, even in mice. We can tell you you can maybe live better and restore some of your function.”
There are some other questionable details about the Ambrosia study. Science reports Ambrosia is charging participants $8,000 each to participate — a setup that’s ethically dicey but not outright forbidden by the Food and Drug Administration. Also odd: The trial has no placebo group, so the insights it can publish will be limited. Plus, the study hasn’t limited its recruitment to the very old. It’s open to all people over the age of 35.
Parabiosis may be better suited for human studies where there is a discrete, measurable condition as a target — like Alzheimer’s.
There is a trial by a company called Alkahest that’s looking at whether plasma transfusions can improve cognitive function in people with dementia. It’s not charging participants to enter.
But even here, there are practical limitations: “If we were to use blood transfusions for Alzheimer’s, I don’t think there’s enough young blood out there to treat every single person,” Villeda says. (He is on Alkahest’s scientific advisory board.)
There’s something about blood that’s alluring, mystical even, drawing people to this research. That’s why it’s even more important to avoid hype.
“I want to make sure that as we do start thinking about therapeutics and applications that we do it in a manner that gives us the highest probability of success,” Villeda says. “It would be so sad if this is something that can translate, yet because it is not [researched] in an appropriate way, we never find out. “