Dr. No resigned.

Trump called him a "wonderful man" and said he'd "lead a good life." 

Marty Makary posted his own resignation message touting his accomplishments — the priority review process, the faster approvals, the agency reforms.

He got a dignified exit and a face-saving send-off. The official record will show he left of his own accord.

It will need an asterisk.

The Wall Street Journal reported Friday that Trump had signed off on his firing. The decision was walked back over the weekend. HHS Secretary Robert Kennedy reportedly made the final call. 

They showed him the door, and they let him walk through it himself.

What got him pushed out were things like faster vape approvals and a safety review he was slow-walking. But there was also internal dysfunction and staff revolt. 

What doesn’t seem to be as much of a proximate cause in the news were his FDA’s rejections of breakthrough lifesaving drugs like gene therapies for Huntington's patients, watching an agency walk away from something they had previously agreed to, or the melanoma patients with months to live whose therapy got rejected twice. 

Those generated the public pressure that built up over the past year. They didn't pull the trigger. It was fruit-flavored vapes and abortion pills that did it.

Consumer products and the culture war ultimately mobilized the political will to remove an FDA commissioner. It didn’t get mobilized by therapies for the dying.

Still a good thing though.

The FDA will hopefully have a lighter touch after Makary’s exit, and maybe we can see breakthrough, lifesaving therapies reach patients, but it still doesn’t fix a problem the agency has always had.

The Man in the Left Lane

In the early 1980s, traffic engineers on the Capital Beltway noticed that every weekday morning, miles of traffic would stop dead in the same lane at the same hour. It wasn’t construction or an accident that caused a wall of brake lights.

There was this particular man. He got on the same on-ramp every morning. He'd move to the extreme left lane. He'd set his cruise control at exactly fifty-five miles per hour, and he'd hold that lane for seventeen straight miles.

He was obeying the law. To him, the drivers piling up behind weren't. 

As he told the Washington Post in a 1984 profile, the speeders were "stealing the road from those of us who pay taxes."

His name was John Nestor. The citizens of Washington coined a verb in his honor — Nestoring — for self-righteously blocking traffic in the name of the rules.

Where did John Nestor work?

The Food and Drug Administration. 

Of course.

He was a senior reviewer in the division that approved cardiac and renal drugs. 

His drug approval safety record was perfect, since he approved nothing.

When the FDA tried to transfer him out of a job where his temperament was costing patients their lives, Ralph Nader's Health Research Group sued to have him reinstated — because he was protecting the public interest. From cures, presumably. The lawsuit succeeded, and Nestor stayed.

That guy is still there. Different name, different suit. The mindset has never left us.

Only the cars piling up behind him aren't just commuters running late.

They're patients dying.

Technocrat Says Quiet Part Out Loud

In 1992, FDA Commissioner David Kessler told an audience exactly what he thought the agency existed for.

"If members of our society were empowered to make their own decisions," he said, "then the whole rationale for the FDA would cease to exist."

The man running the agency stated, on the record, that the entire institutional rationale depends on patients not being allowed to make their own choices.

That principle organizes the agency's behavior across every decision it makes. It's why a dying cancer patient can't access a therapy that might save them. It's also why a healthy adult couldn't decline a vaccine they had questions about during COVID.

How the Sausage Got Made

Big Pharma didn’t capture the Makary FDA. Philanthropy did.

Arnold Ventures is a $4.3 billion outfit founded by hedge fund manager John Arnold. Its policy program advocates for what it calls "evidence-based" healthcare, which, in practice, means restricting access to treatments by demanding randomized controlled trial standards that smaller companies and rare disease populations often cannot meet.

In December 2023, Arnold Ventures submitted a formal comment letter to the FDA arguing that natural history evidence, real-world evidence, and external controls should be restricted as confirmatory evidence for drug approvals. Katherine Szarama drafted the letter; she was the then-Director of Clinical Trials at Arnold Ventures.

In May 2025, Makary appointed Vinay Prasad — whose academic research had been funded by Arnold Ventures with a $2 million grant beginning in 2017 — as Director of the FDA's Center for Biologics Evaluation and Research (CBER).

In October 2025, Prasad hired Szarama as his Acting Deputy.

Three weeks later, uniQure disclosed that the FDA "no longer agrees" with the external control pathway it had aligned with the agency a year earlier for its Huntington's gene therapy. The agency now strongly recommends a sham surgery-controlled Phase 3 trial.

They insisted on a placebo group in the trial as a condition for approval.

That literally means the FDA wanted them to take a control group of sick patients, put them under anesthesia, drill a hole in their heads, and perform fake brain surgery.

In the treatment arm, deliver the gene therapy. In the sham arm, deliver nothing. 

Half the dying patients get the experimental therapy, which might work! Half get the surgical risks to receive nothing.

That is what Szarama's 2023 comment letter looks like when translated from regulatory language into operational reality. The letter cost her nothing to write. The implementation would cost Huntington's patients fake brain surgery for a placebo.

Prasad resigned from the FDA on April 30, his second stormy departure in a year. Richard Pazdur, the career oncology director who has been the institutional voice for drug review standards for two decades, walked away too, citing Makary's leadership as his reason. 

Yes, Makary just got shown the door.

Unfortunately, Szarama is still Acting Director ofCBER.

The hiring chain that installed her is still operational. 

The pharmaceutical industry is signaling that it's "wary about a shakeup," which is industry-speak for "we don't know what this means and neither does anyone else."

What we do know is this: Trump needs Senator Bill Cassidy's support to install a permanent commissioner, and Trump is currently backing a primary challenger against Cassidy in Louisiana. 

The confirmation politics are about to get complicated. The acting leadership could remain in place for months.

These Cars Can't Honk

The cars stuck behind John Nestor in 1984 had a way to express their frustration. They could honk. They could write letters to the Washington Post. They could coin a verb.

The patients stuck behind the modern Nestors at the FDA can't honk.

They die quietly, one at a time, in oncology wards and pediatric hospitals and at home in hospice care.

Eventually, you'll be in that traffic jam too. So will I. So will everyone reading this. The only question is which drug you'll be waiting for, and whether the people in the left lane will let it get built.

Here is what this means for your portfolio. The biotech sector is reacting to the resignation news, and parts of that reaction are justified. The political pressure that led to Makary's exit is real, and it will discipline the next commissioner, regardless of who Trump picks. 

But the bigger move, the one that re-rates the small-cap rare disease names that have been Nestored to death over the past year, comes when Szarama is replaced, and the Arnold Ventures framework is dismantled.

Wrap Up

Dr. No got shown the door this morning. He resigned, officially. He left like a gentleman, according to the President. 

He'll lead a good life.

The machine he hired is still sitting in the driver’s seat.

And the people who built the framework — the philanthropy, the funded academic, the policy expert turned regulator — are still in the room, still running the show, still writing the rules they wrote before they got the jobs that let them enforce them.