Level 2 · BiohackingBiohacking UpgradesThe regulatory gate every longevity drug has to pass — what gets approved, on what evidence, and at what safety bar.
Live Beyond · A Great Mind on the Quest
Larry Callahan
FDA scientist for twenty years · retired 2024 Twenty years inside the agency that decides what medicine reaches you · Washington, DC
Larry Callahan is a chemist who spent roughly twenty years as a scientist at the US Food and Drug Administration — the agency that decides which drugs reach the public, and which don’t. He retired in the summer of 2024, weeks after we sat down with him.
He is not a longevity researcher. That is exactly why his voice matters here. Almost every scientist on our quest eventually runs into the same wall: the regulator won’t approve a drug for aging, because aging isn’t a disease. Larry, who spent two decades on the other side of that wall, says the wall isn’t where everyone thinks it is.
Under the legislation the FDA works from, a drug does not have to target a named disease. If it demonstrably improves and maintains a person’s function — if they can still walk, still live independently, still stay out of the hospital at ninety — that is already an approvable endpoint. What changes is the evidence you owe: treating healthy people carries a far higher safety bar than treating the sick.
He is equally candid about what’s broken. Trials cost too much and take too long. Data from failed trials disappears, so nobody learns from it. Elderly patients are routinely on six or more drugs, and no one can untangle what’s causing what. And in longevity specifically, he warns, there is real money and real charlatanry.
US Food & Drug AdministrationDrug approval & regulationClinical trial reformFunction as an endpoint
Washington, DC · June 2024
On the grass outside the FDA
Where we met
We came to Washington to ask the question every longevity scientist had raised with us — and to ask it to someone who had actually sat inside the agency. We visited Larry’s FDA offices, then walked out and sat down cross-legged on the grass. He was two months from retirement, in a baseball cap, entirely unguarded. It became one of the most quietly consequential conversations of the whole quest.
The FDA
Washington, DC
Twenty years of decisions about what medicine is allowed to reach the public.
On the grass
June 2024
Cross-legged in the shade, weeks before he retired — and completely straight with us.
The Capitol
Capitol Hill
Where the legislation he kept pointing to is written — and where it could change.
“Next to going to war, the decisions that the FDA makes are probably the most important decisions the government makes.”
— Larry Callahan, Washington, DC
On the quest
A morning in Washington
The conversationTwo men on the grass, no press officeArrivingUS Department of Health & Human Services · FDA
In his words
You don’t have to call it a disease
“You don’t need to call aging a disease to get drugs approved that will prolong health.”
Larry Callahan · US Food & Drug Administration
If you improve the function of somebody — if they can walk farther and keep walking as they age — that’s a path. That’s in the legislation.
Larry Callahan
When you’re treating healthy people, you have a much higher safety bar than when you’re treating a person with a disease.
Larry Callahan
You don’t have a God-given right to do a clinical trial, even if you’re a multi-billion-dollar pharmaceutical company. Society has to benefit from it.
Larry Callahan
Scientists are a little bit like lemmings. Once a technology comes out, everybody jumps on it — whether it’s CRISPR or mRNA.
Larry Callahan
In his own words
Straight from the interview
From our conversation in Washington — the regulatory door that’s already open, the thing that makes it harder than it looks, and what he wished for us as we left.
His view: the door is already open
The longevity field keeps campaigning to have aging reclassified as a disease. Larry says that campaign may be aimed at the wrong target. Function is already an approvable endpoint under the legislation — keep someone walking, independent and out of assisted living, and you have a case.
“You don’t have to be against a disease to get a drug approved.”
Washington, DC · from the interview
The catch: healthy people raise the bar
The trade-off is safety. Treating well people is closer to a vaccine than a cancer drug — the tolerance for harm is far lower, and most older patients are already on six or more medications, which makes any new side effect nearly impossible to attribute.
“We have people really overmedicated, if anything, in this country.”
Washington, DC · from the interview
His wish for the quest
Asked what he wished for Marek and Aleksander for the rest of the journey, he didn’t talk about science. He talked about honesty — and about how much money is now circling the longevity field.
“Make a good movie. Get something good out there — and be truthful. There are a lot of charlatans in the longevity field.”
Larry retired from the FDA in 2024 — send me a personal link if he’d like one here.
From the conversation
Larry Callahan, in his words
Video interview
The video interview is coming. Recorded interviews go live after the launch of the film & series Live Beyond.
Selected passages from our conversation with Larry Callahan — Washington, DC, June 2024. Lightly edited for readability.
On what the FDA actually does
Larry Callahan“Basically, to support and improve public health — approve drugs that will hopefully have more benefit than risk. They also monitor the food chain. About twenty to twenty-five percent of the US economy gets monitored by the FDA. Food additives, veterinary products, tobacco. I frequently say that next to going to war, the decisions the FDA makes are probably the most important decisions the government makes — because if they approve a drug they’re really giving a company billions of dollars, and they’re putting public health at risk if they make a mistake.”
On whether aging has to be called a disease
Marek Piotrowski“These longevity drugs are supposed to let us age more slowly, so the diseases come later. They act against disease, but not directly. So what’s the path?”
Larry Callahan“You don’t have to be against a disease to get a drug approved. If you improve the function of somebody — if they can walk farther and maintain their walking as they age, when they’re ninety — that’s a path. You don’t have to call aging a disease to get a drug that may prolong life or promote healthspan. That’s in the legislation for the FDA.”
On the higher bar for treating the healthy
Larry Callahan“When you’re treating healthy people you have a much higher safety bar than when you’re treating a person with a disease. It’s like a vaccine — vaccines have a much higher safety bar than, say, a cancer drug. The more severe the disease, the more risk you can take on safety. There’s a balance there.”
On what actually keeps older people out of hospital
Larry Callahan“One of the biggest side effects of drugs is getting you dizzy. If you’re dizzy you fall, you break a hip, you end up in the hospital, you catch pneumonia, you die. That’s a common pathway. So one of the most important things for somebody who’s elderly is actually: can they walk right? And we might not monitor that as well as we should.”
On AI and the data problem
Larry Callahan“The important thing is to get good data. If you don’t have good data, AI is not going to do much. We’re still basically in the twentieth century — most of what we get from industry arrives as PDFs. Even the scientific literature isn’t structured. A paper is a delay of data; by the time you publish, sometimes the data’s old. It’s really the data that matters.”
On making trials faster — and public
Larry Callahan“We have to find a way. Platform trials — you set up a bunch of endpoints and run several drugs against them in parallel. And clinical trials should be completely transparent. Before you go in, release the physician’s brochure and the preclinical data so other people can look at it. If you’re a cancer patient, you’re putting your life on the line and you can’t really make an informed decision. You don’t have a God-given right to do a clinical trial, even if you’re a multi-billion-dollar pharmaceutical company. Society has to benefit from it — and if the data never gets out, society doesn’t.”
His message to Aleksander’s generation
Marek Piotrowski“He's eighteen. What would be your message to the younger generation about their longevity?”
Larry Callahan“Take care of yourself, because you’re going to have to take care of us. Unless something is done, you’re going to spend a lot of your life looking after your older parents. Live healthy — a lot of us wasted some of our youth not living healthy. And respect life.”
What he’d tell his own eighteen-year-old self
Larry Callahan“Don’t drink sugary drinks. I drank Mountain Dew for years — I’m probably fluorescent inside. I was a chemist and I wasn’t that careful. I worked with some really toxic chemicals. You just don’t realise what you’re doing. You have this idea that you’re going to live forever, that things can’t hurt you. But they can.”
His wish for the quest
Marek Piotrowski“What would be your wish for me and Aleksander, for the rest of our quest for longevity?”
Larry Callahan“Make a good movie. Get something good out there to change people’s habits — inspiration. And be truthful. There are a lot of charlatans in the longevity field trying to make a lot of money. What you’re doing is really important.”
More passages from the full interview will be published here.
Continue the quest
More minds on the quest
Larry sits at the Biohacking Upgrades level of the Longevity Map — the gate every intervention has to pass before it reaches you. Here are others on the quest, and the full cast of 100+.
