Ambrosia Health and the Downsides of Developing Marginal Therapies

One of the many good reasons to be guided by the SENS approach to aging, meaning a focus on repairing molecular damage as close to the causes of aging as possible, is that it has a greater likelihood of resulting in a viable therapy. Benefits should turn out to be sizable, broadly applicable to many age-related conditions, and reliable. The present best example of the type is provided by senolytic therapies that clear senescent cells. The more prevalent and popular strategy of tinkering with metabolism or adjusting the late-stage, dysfunctional disease state, throwing signals into the mix to override cellular reactions to damage, or upregulate stress responses, and while hoping for the best, has a high failure rate in larger human trials. With few exceptions, benefits tend to be unreliable, narrowly applicable to just a handful of conditions, and small.

Unfortunately, once development has reached the stage of a funded company focused on developing a particular therapy, it is hard for anyone involved to back down and admit failure to achieve good results. A few companies, Ambrosia and Alkhahest, are currently in this position when it comes to the use of blood and plasma transfusions to try to recreate the benefits observed in parabiosis studies. In these animal studies, the circulatory systems of old and young mice are linked; the young mice suffer accelerated measures of aging and they old mice gain some reversal of measures of aging. Unfortunately, research completed after these companies were established, and then the data generated by the companies themselves, shows that there is nothing here of interest. If there is an effect resulting from transfusion, it is small and unreliable. For one, transfusion is a terrible way to try to recreate the effects of a complete joining of circulatory systems, and secondly the evidence now strongly indicates that benefits in the old mice in parabiosis studies are more a matter of dilution of harmful factors in old blood rather than the delivery of beneficial factors in young blood.

The media are sharks and will cheerfully build a narrow pedestal for a company and its founders one day, uncritically accepting all company statements as fact without challenge, and then turn on a dime to knock all it down the moment that the data fails to live up to unrealistic expectations. They will be unkind about failure, regardless of how deserving the people involved actually are; they will mix together all possible reasonable and unreasonable accusations while constructing their narrative, as illustrated in today's article below. This is another thing to bear in mind when considering what sort of medical biotechnology to pursue, and how to pitch it at the outset.

The article here assembles a grab-bag of complaints about Ambrosia, some of which are valid and useful, and some of which are quite pernicious, such as the leading presentation of the death of an aged trial participant, or the way the authors played the public opinion game with blood banks. Most of the technical complaints about lack of effect for the therapy could just as well be leveled at Alkahest, but Ambrosia is an easier target given their non-traditional approach to trials and present diminished position. For my part, I see nothing wrong with patient paid trials that are responsibly conducted. It allows for tests of potential therapies that might otherwise never happen. There is an unseemly hostility to this approach to trials, sad to say, both in the research community and in the media. Objections on that front when a company fails to produce good results are irrelevant and unhelpful. On the other hand, calling out the founders of companies that continue with a failed program because no-one has the moral courage to admit failure and call a halt is a good thing, and it is a pity that it isn't done in most such cases.

Jesse Karmazin, the founder of the startup Ambrosia, had a pitch journalists couldn't resist: For a fee, he could help his clients combat aging and its related ills with infusions of blood plasma from the young. Teen donors, vampiric undertones, a serious-sounding study, an $8,000-per-person price tag and rumors that venture capitalist Peter Thiel might be interested earned Ambrosia more than 100 press mentions in just two years.

But despite declaring the study a success and announcing plans this week to accept new clients, Karmazin never showed any proof that the transfusions actually helped people. In the media, he touted impressive results, but almost a year after his study officially concluded in January 2018, he hasn't released them. Scientists have criticized the study as flawed and the procedure as medically unnecessary and not without risk; in rare cases, transfusion complications can be fatal. One of the doctors Karmazin hired had previously been disciplined by a state medical board for unprofessional conduct.

Karmazin himself cannot legally practice medicine in any state; he is explicitly prohibited from practicing in Massachusetts by authorities. Ambrosia's president and chief operating officer quietly left the company in late December, leaving Karmazin as the sole employee. And the only patient who spoke publicly about Ambrosia's transfusions - treatments he hoped would help him live healthier into old age - died at 65 after going into cardiac arrest.

We found that at least some of Karmazin's young plasma came from a nonprofit blood bank in Texas that recruited teenage donors for "saving lives," but noted on a consent form that their blood components could also be used for "any other medical purpose." The bank abruptly decided to stop selling young plasma after we reached out, according to an employee email.

Ambrosia, which declined to comment on whether the company has any investors, is only one of many firms investigating how to help people feel younger for longer. But Ambrosia's ability to attract paying clients and years of positive press coverage - without providing scientific data to back up its claims - shows just how easy it can be for promises to outpace the research when Silicon Valley gold-chasing mixes with Americans' fear of death.