It sounds like a dystopian, vampiric fantasy: Take the blood of strapping young things, insert it into tired, aging bodies, and voila! The fountain of youth!
That might seem like the wild plotline of a bad horror flick. But parabiosis—the process of taking the blood of a young person and transplanting it into an older person—attracted a warning from the FDA on Tuesday afternoon, when it urged the public to be cautious of companies collecting plasma donations from young people—some as young as 16—for infusions purported to help treat, or even cure, Alzheimer’s, post-traumatic stress disorder, and, of course, aging.
“We have significant public health concerns about the promotion and use of plasma for these purposes,” the statement read. “There is no proven clinical benefit of infusion of plasma from young donors to cure, mitigate, treat, or prevent these conditions, and there are risks associated with the use of any plasma product.”
“We strongly discourage consumers from [pursuing] this therapy outside of clinical trials under appropriate institutional review board and regulatory oversight,” the FDA added.
The FDA statement didn’t name any specific companies. But one of the best-known blood brokers, a company called Ambrosia, immediately announced that it would end its treatments after the FDA statement. The company previously charged between $8,000 to $12,000 for dubious blood transfusion services, which it billed as “clinical trials.”
While it sounds like sci-fi, the theory of parabiosis is strikingly straightforward: Blood, like skin and cells and organs, ages. Younger blood cells, then, should be more active, able to reproduce and replenish much more quickly and vibrantly than their older counterparts.
The theory has been floated among scientists since at least 1864, when a physiologist named Paul Bert invented the term as he studied how circulatory systems developed. In the 1930s, Clive McCay, a biochemist and gerontologist at Cornell University, became a critical figure in the study of aging, noticing that caloric restriction helped extend the lives of aging rats. He also began experimenting on taking the blood of younger rats and putting it into older rats. Around the same time, a physician, Bolshevik Alexander Bogdanov, tried the procedure on himself, injecting the blood of a student infected with malaria and tuberculosis. He died.
By the 1950s, parabiosis had become a vestige of science, a Frankenstein-ish experiment made more morbid by a spate of rat deaths from parabiotic disease, possibly as a result of their tissue rejecting transfused blood. But experiments at Cornell found that sewing together an older rat and a younger rat—so that they shared organs and blood—showed marked improvements in the elderly rat.
Those crude mid-century experiments inspired a pair of Stanford University researchers at the dawn of the millennium. Irving Weissman and Thomas A. Rando came across the Cornell experiments and decided to replicate them for a 2014 study in Nature. After five weeks, they found the elderly mice (when sewn together with younger ones) were back at it, with muscles rejuvenating like they were young, brain cells replicating quickly and efficiently, livers and hearts pumping as if they were new.
“We can turn back the clock instead of slowing the clock down,” Toren Finkel , director of the Center for Molecular Medicine at the National Heart, Lung and Blood Institute, told Nova. “That’s a nice thought if it pans out.”
Subsequent studies have been touted among the anti-aging evangelists as proof that young blood works, but have been rife with controversy. In 2005, Weissman and Rando teamed up with Irina and Michael Conboy at the University of California at Berkeley. Their bombshell report in Nature purported to find that the blood transfusion technique helped repair and regenerate aging muscles in mice.
But in 2016, the Conboys published another study in Nature that questioned whether parabiosis could work if the old mice and young mice weren’t literally sharing organs. The results weren’t so promising.
In the 2016 remix of the study, the team developed a device that transferred blood between the young and old mice without fusing their bodies together. This device was used on eight mice—four old, four young, each age group giving a corresponding mouse of the other age group blood until they had half of the original blood they started out with. Four other pairs of mice were controls, with young mice switching blood up with other young mice and old mice exchanging with fellow old mice.
The muscles of old mice with young blood showed signs of improvement almost immediately, though their brain cells showed almost no change. The fate of the young mice, however, was problematic and worrisome: their liver and brain cells deteriorated, and they showed signs of inflammation.
Good for the older mice—but at what cost? Conboy told The Verge that the study confirmed parabiosis wasn’t what it was cracked to be. “You risk a catastrophic immune response [if blood and tissue reject each other],” Conboy said. “When people do transfusions, usually the alternative is that they’re going to die. To do it just to work yourself up and make yourself seem younger, that’s pretty risky.”
The pair of parabiosis studies highlights one of the biggest problems in young blood experiments: the fact that they are almost entirely done on mice. Translating results from mice to humans is a huge scientific leap, one that could be even more dangerous—even deadly—for humans, particularly if they are teenagers. Most FDA clinical trials are wary of jumping from rodent to human in testing drugs on humans; using results that are done on just a handful of mice as proof of human capability is unheard of. And fusing mice to exchange blood for one person’s youth at the expense of the other person’s health is ethically, legally, and medically dubious.
In fact, teenage blood donors are 14 times more likely to face complications, according to this piece in Pediatrics:
The Murky Business of ‘Young Blood’ Startups
That hasn’t stopped companies like Ambrosia from building a Silicon Valley fanbase among those looking to “hack” or “disrupt” death and aging.
Ambrosia described its work as being part of a clinical study. The designation allowed the company to work with less regulatory oversight. Ambrosia charged trial “participants” $8,000 for a liter of blood plasma, and $12,000 for two liters. Karmazin defended the prices to MIT’s Technology Review in 2017, saying they were to cover lab costs, not to make a profit. Yet the outlet estimated that a liter of plasma cost $1,000 on the open market, and a set of blood-testing chemicals, $3,000. Those estimated prices would theoretically net Ambrosia a 50-percent profit on all its one-liter transfusions.
Another emerging organization is the Young Blood Institute, a group promoting young blood transfusion. According to a profile in STAT, trials have no control groups and charge participants $285,000 per person.
S. Mitch Harman, a principal investigator with the Young Blood Institute and a chief endocrinologist with the VA in Phoenix who has conducted aging studies, told The Daily Beast in an email that the science is much more established, citing a study as recent as one published last month in JAMA Neurology that showed how the plasma of young mice restored the memory of elderly mice.
Harman explained that YBI differs from what companies like Ambrosia are thought to do because they focus on plasma, the yellowish part of blood that carries blood cells and proteins.
“The basic design of the YBI studies is to exchange plasma of elderly volunteers,” he said, referring to the process of plasmapheresis. After YBI performs plasmapheresis, the institute measures a number of factors: “immune system function, circulating cytokines, hormone secretion, glucose metabolism, cognitive capacity and biochemical markers of AD, muscle function, body composition, and others,” according to Harman. Harman said the research is overseen by the Western Institutional Review Board, a group of academics and clinicians overseen by the University of California.
Mark Urdahl of the Young Blood Institute explained that transfusion actually means “taking away old plasma and replacing it;” in the case of the Institute’s research, that replacement for transfusion takes the form of “albumin/IVIG, purified plasma components manufactured by Grifols and Octapharma, plus saline (water with salt/electrolytes).”
Urdahl added that what the institute was researching should not be considered blood transfusion.
“Transfusion, as in plasma exchange or plasmapheresis, differs from infusion,” Urdahl wrote in an email to the Daily Beast. “Infusion does not take anything away but simply adds a fluid; transfusion removes the old plasma and replaces it with either 5% albumin (and typically IVIG) or Fresh Frozen Plasma (FFP) or Liquid Plasma (not frozen).”
But the numbers of “study participants” and clients (and the line between the two) has not always been clear in other efforts.
Ambrosia’s Karmazin told the Technology Review that he and David C. Wright, a California doctor, had infused 25 patients with young blood by Dec. 15, 2016 as part of their trial. The trial could include as many as 600 paying participants. By August 2017, the Guardian reported Karmazin had his 600 clients (“with a median age of 60”). If accurate, the figure represented a 2,400 percent increase in patients served over eight months, when Karmazin had previously described himself as working with a single doctor. The Guardian also described 65 people as having signed up for a clinical trial with Ambrosia. (This latter figure seems more achievable, especially since Ambrosia describes all its work as clinical trial.)
In January 2018, Ambrosia concluded a clinical trial, allegedly of 200 participants. Although Karmazin registered that clinical trial with the government, he has still not made its conclusions public, other than to call them “very positive” in an interview with Business Insider.
In September 2018, Ambrosia’s then-chief operating officer David Cavalier told Business Insider the company had served nearly 150 people. (Cavalier has since left the company.) But by December, the number had shrunk again, with Karmazin telling the Huffington Post he’d had 104 paying clients.
Equally opaque are the company’s staffing and centers of operation. After Cavalier’s departure, Karmazin appears to be the only person listing himself as an Ambrosia employee on LinkedIn. Karmazin previously told the Huffington Post that he and Wright had a falling-out before the conclusion of a clinical trial in 2018.
In fact, none of Ambrosia’s alleged clinics list their addresses publicly. Until the FDA released its warning against young blood treatments on Tuesday, Ambrosia’s website described itself as operating out of Phoenix, Arizona; Los Angeles, California; Tampa, Florida; Omaha, Nebraska; and Houston, Texas. But none of the alleged locations list an address, and none of the clinics appear in web searches for businesses in those cities.
When Omaha’s World-Herald asked Karmazin about his alleged offices in the city, he declined to reveal their location, citing “unwanted visitors.” He claimed patients would learn the address after they signed up. Newspapers from other alleged host cities also failed to provide an address. The Houston Chronicle’s write-up of Ambrose only cited a Business Insider report that claimed Ambrose operated out of Houston; the report used pictures of people giving blood at unrelated blood drive.
The company made headlines in late 2018 when it announced plans to open a New York City facility that year. Despite that free publicity, the New York clinic never materialized. Journalists have only documented Ambrose transfusions taking place at Wright’s clinic outside Monterrey, California. And even those come with a caveat. Wright, Karmazin’s erstwhile partner, runs a transfusion center, where he administers vitamins and antibiotics intravenously. In 2015, Wright received an official reprimand from the Medical Board of California for negligence and failure to keep accurate records.
According to court documents in that case, Wright prescribed a client six weeks of daily antibiotic IV drips for a tick-borne illness. Both his diagnosis and treatment were wrong. None of the lab tests he ordered revealed the illness, and the six weeks of daily IV drips were “neither the generally accepted modality [...] nor the recommended treatment duration” for the illness, according to court records. The patient started experiencing rashes, abdominal pain, nausea, vomiting, and fevers, which were not correctly reflected in Wright’s records. Eventually she went to an emergency room, where she was diagnosed with a bacterial infection, a possible result of the IV drips.
A New Scientist reporter who observed the Ambrosia-brand transfusions that took place in Wright’s office said one patient suffered an anaphylactic reaction that left Wright “visibly shaken.”
Karmazin has had his own scraps with the medical profession. In 2015 he launched xVitality Sciences, a blood plasma transfusion company offering services outside the U.S. The venture cratered quickly. He fell out with U.S. medical professionals shortly thereafter. A licensed psychiatrist, he signed an agreement in February 2016, which barred him from practicing medicine in Massachusetts. Although a document does not reveal the circumstances of the agreement, the executive director of the Massachusetts Board of Registration in Medicine told the Huffington Post that the deal was unusual.
Harman added that obtaining blood from teens was not an option, at least with the Young Blood Institute. “So far as I know, no one is suggesting obtaining plasma from ‘teenagers’ (who would be below the age for consent to participate in such research),” he said. “However, to maximize potential benefits to recipients, plasma from healthy young adults (20s to early 30s) probably would be optimal, since aging is a continuous process that begins as soon as maturation is complete.”
Harman said he envisions the YBI studies as the way forward from the young blood companies that have dominated the news.
“I regard them as a first step on a long path of discovery,” he said. “Personally, I don’t visualize millions of people undergoing plasmapheresis every year in order to prevent or reverse aging. What we really need to know is the identities of the critical soluble factors so we can come up with cheap and easy ways of clearing the ‘bad stuff’ from the circulation and supplying the ‘good stuff,’ likely produced by the same kind of genetically engineered organisms that have allowed us to produce human insulin and human growth hormone so cheaply.
“Then we would really have ‘anti-aging’ for all.”