Jonathan Howard and Wendy Orent call this week their "Red Wedding": within days, FDA Commissioner Marty Makary resigned, Vinay Prasad was pushed out of CBER, Tracy Beth Hoeg was fired, and Senator Bill Cassidy lost his Louisiana primary. The hosts argue this is not a tragedy but a long-foretold collapse — a group of physicians who built careers as COVID-era contrarian podcasters discovering that running a regulatory agency is fundamentally different from posting about one.

Howard works through the wreckage: Makary's reported approval of flavored nicotine products days before his ouster, the FDA's treatment of the rare disease community, the leaked memo claiming pediatric COVID vaccine deaths that career staff refused to sign off on, and the broader pattern of "regulatory whiplash" that drove the agency into dysfunction. The episode then turns to who is still standing — Jay Bhattacharya at NIH, Robert F. Kennedy Jr. at HHS — and what Kennedy is reportedly doing to vaccines from behind the scenes via Martin Kulldorff's review effort.

Throughout, the hosts return to a single thesis: the skills that made Makary, Prasad, Hoeg, and Cassidy famous during COVID — opinion, tweeting, posturing — do not translate into running institutions, and the medical commentators who vouched for them (John Mandrola, Adam Cifu) have lost any remaining credibility.

Key Topics Discussed Bill Cassidy's primary loss and the cost of the Kennedy confirmation vote

Cassidy's earlier vote to convict Trump after January 6 followed by his decisive vote advancing RFK Jr. as HHS Secretary.
Howard and Orent's view that Cassidy's promise to "keep Kennedy in line" was hollow from the start.
What Cassidy's defeat signals about Trump's grip on the Republican base in Louisiana — and the hosts' read that his lame-duck status may give him cover to block the next round of HHS nominees.

Marty Makary's resignation and the "worst FDA Commissioner in 25 years" framing

The Stat News piece characterizing Makary's tenure, and the reporting that flavored nicotine was the precipitating issue with Trump's tobacco-industry donors.
Howard's counterpoint: Makary reportedly approved a batch of electronic nicotine delivery systems (ENDS) on May 5, 2026 — the weekend before he resigned — undercutting the "principled stand" narrative.
The pattern of selfie videos, public-facing performance, and what former FDA staff describe as hostile management of career scientists.
Makary's pre-FDA record: the "medical error is the third leading cause of death" claim, Omicron as "nature's vaccine," "Omicold," herd immunity calls in May 2021, and the Nazi-bioweapon Lyme disease theory amplification.

Vinay Prasad, regulatory whiplash, and the rare disease community

How Prasad's stated preference for randomized controlled trials translated into rejection of rare disease therapies — and the disconnect between calling for RCTs on Twitter and the practical impossibility of running them for small patient populations.
Right-to-try advocates, the libertarian wing of MAHA (Senator Ron Johnson), and why they turned on Prasad.
Howard's point: Pfizer's halted COVID vaccine RCT in 50–65-year-olds is the case study — the trials Prasad demanded couldn't actually be enrolled.

Tracy Beth Hoeg, the leaked pediatric deaths memo, and the Maryanne Demasi interview

Hoeg's insistence she was fired, not resigned, and her interview with Brownstone Institute–adjacent journalist Maryanne Demasi.
Her claim that the chaos at the FDA was "created by the media" rather than real.
The memo alleging 10 pediatric deaths from the COVID vaccine that career FDA staff would not sign off on — and Howard's contrast with the J&J/thrombosis response, where nine deaths produced immediate, transparent action.
Hoeg's role in the Denmark-style vaccine schedule rollback memo alongside Makary.

The Makary–Prasad ZDoggMD clip on FDA "vindictiveness" — and the irony

Audio pulled from a pre-appointment Prasad/Makary appearance describing the FDA as "erratic," "capricious," and politically pressured.
Howard's read: every criticism they leveled at the Biden-era FDA describes their own tenure — political pressure from Trump, demoted career staff, inconsistent standards.
The Peter Marks / Marion Gruber / Phil Krause booster episode reframed in light of what followed.

John Mandrola, Adam Cifu, and the cost of vouching

Mandrola's "Can We Give the New FDA's Leadership a Chance?" piece a year earlier — and the line about Prasad and Makary inducing companies to run proper RCTs, set against Pfizer's halted trial.
Howard's account of an email exchange with Cifu following Cifu's visit to NYU — Howard's offer of a serious content-level conversation, and Cifu's decline.
The broader "medical conservatives" project and what the hosts argue has happened to its credibility.

Jay Bhattacharya, NIH, and the resignation letter from departing staff

The letter from a senior NIH scientist on Bhattacharya's leadership — political termination of grants, deals institutions are making to recover funding, and Bhattacharya's silence.
Howard and Orent's read on Bhattacharya's visible deterioration and his retreat into Great Barrington nostalgia.

Kennedy's behind-the-scenes vaccine review and Martin Kulldorff

The New York Times reporting (Christina Jewett and Sheryl Gay Stolberg) on Kennedy's vaccine inquiry being led by Kulldorff.
Howard's pushback on the framing of Kulldorff as merely "a critic of restrictions and mandates" — and the 2020 record of his herd-immunity-through-infection advocacy, including his Stockholm "almost at herd immunity" claim in April 2020.
The hosts' concern that the COVID amnesia project lets pandemic-era pro-infection figures re-enter regulatory power with their record sanitized.

Casey Means, Surgeon General nomination withdrawal, and MAHA fracturing

The withdrawn Surgeon General nomination and what it signals.
The Robert Malone vs. Makary public falling-out over the unreleased pediatric deaths data.
Why the MAHA coalition — held together by shared COVID grievance — is coming apart now that COVID has receded from headlines.

Notable Moments

On Cassidy: "He betrayed his oath as a physician, he betrayed the American people, and he's going down into the ignominious dust." — Wendy Orent

On the Makary–Prasad–Hoeg trio: "The same skill sets that catapulted these guys to power — essentially being excellent podcasters — do not translate into leading a government agency of tens of thousands of employees that regulates 20 percent of the US economy." — Jonathan Howard

On the legacy: "These guys are now cautionary tales for medical students. I would love to teach a course called 'Be the Opposite of Bill Cassidy, Marty Makary, Vinay Prasad, and Tracy Beth Hoeg.'" — Jonathan Howard

On Bhattacharya: "His soul has been totally corrupted by the people who he teamed up with. You also see it in his face. He's not the same person that took the position." — Jonathan Howard

References Mentioned in the Episode

Stat News — "Why Marty Makary Was the Worst FDA Commissioner in 25 Years"
Vinay Prasad's 2016 Stat News rebuttal of Makary's "medical error" claim
David Gorski (Science-Based Medicine, 2016) — rebuttal of the medical-error-as-third-leading-cause-of-death claim
Jonathan Howard, Science-Based Medicine — recent piece compiling Makary's COVID-era statements
New York Times — Christina Jewet...