Playing Poker With Marty Makary

Populism, policy, and poker: Makary’s volatile hand at the FDA

Cold Open – Ante Up at the Silver Springs Saloon

It is 1:43 a.m. on a Wednesday, the air in the Silver Springs Saloon poker room trapped somewhere between Marlboro Red and Lysol Citrus, with notes of desperation and Ben‑Gay. At the six‑max $2‑$5 table sits a newly crowned dealer: Dr. Marty Makary, fifty‑something transplant surgeon, pandemic pundit, and—since last month—commissioner of the Food and Drug Administration. He riffles the agency's 18,000‑employee payroll like a stack of tournament chips; phones flicker with RFK Jr. tweets; a slot machine coughs up three raccoons and no jackpot. The hand is dealt, and the question—bluff or true believer—hangs over the felt like neon sweat and deferred regulations.

Seven days after his stealthy swearing-in (the White House press office somehow "forgot" to blast the announcement), Makary had already signed the execution order for FDA's vaccine czar Peter Marks. By April 2nd, an HHS memo confirmed approximately 3,500 FDA positions vaporized—poof!—with Makary claiming that the cuts merely excised Bureaucratic Plaque from the regulatory arteries. A week later, RFK Jr.—the administration's supplement-hawking Supplement Secretary—described the remaining FDA employees as "sock puppets” for pharma.

Today is May 7th; and the dealer's cards are on the felt. Someone’s already spilled Bulletproof coffee on the rulebook.

Pocket Kings – Early Crowd‑Pleasers & the Purity Pledge

Makary saunters into his Senate hearing holding pocket kings—good cards, but you still need table cred. The guy co-built the WHO’s surgical-safety checklist, a one-sheet intervention that’s measurably shrunk complication rates globally (the type of quiet-but-consequential tweak that rarely gets senators or Substack warriors excited, but maybe should). He wrote The Price We Pay, the kind of health-policy exposé about hospital "chargemasters" and billing horror-shows that actually nudged the dial on price transparency, landing hospital executives under the sort of legislative spotlight they’d happily trade for an IRS audit.

At the hearing itself—imagine it like a slow-motion Capitol Hill Kabuki crossed with a highly formalized first date—Makary methodically puts forth policy planks that are refreshingly free of partisan pyrotechnics. He calmly pitches OTC status for naloxone, EpiPens, and continuous glucose monitors—arguing (not unreasonably) that visible prices on drugstore shelves might act as a kind of fiscal disinfectant for egregious price-gouging. He commits to wrestling patent-thickening maneuvers into submission so generics can actually enter the market sometime before their inventors’ grandchildren retire. He assures the committee he'll run the FDA’s drug-review process under a regime of transparency and institutional integrity, explicitly promising that regulators must “call balls and strikes” visibly, free from cozy corporate entanglements or political meddling.

Then, with dealer-button elan that would make Doyle Brunson proud, he unveiled the NAMs Roadmap—fully integrating non-animal toxicology testing by 2030!—and the crowd cheered as if the mice had already packed their suitcases and bought condos in Tampa. (PETA sent vegan cupcakes, I’m sure).

The NAMs Gambit – Why the Mice Are Still Nervously Applying Lipstick

The April 10th press release generates enough clean-energy hot air to power Texas through August. "A new paradigm," it proclaims. Twenty-first century science replacing nineteenth-century cruelty. The roadmap promises to "reduce animal use" and "accelerate cures and meaningful treatments for Americans"—paired goals with the emotional heft of puppies and cancer kids.

But inside FDA's Center for Drug Evaluation and Research, veteran toxicologists exchange thousand-yard stares. One reviewer (I'll call her "Jxnxt" to protect her vowels and job) mutters to me that six-month monkey studies are "not leaving this building unless you show me knockout target validation and a choir of PK chips singing '99 Bottles of Bioavailability' in perfect harmony." The roadmap, she says, is aspiration wrapped in PR, then deep-fried in wishful thinking; three-month waivers for monoclonals are Maybes-On-A-Good-Day, not Automatic Passes.

Digging into the actual Roadmap details reveals a mouse-sized squeak beneath the elephant-sized announcement. A handful of pilot use cases are outlined: organ-on-chip platforms still climbing the validation ladder, AI models built on animal-era training sets, and case-by-case waivers for monoclonals with near-celibate safety profiles. The language is classic FDA: “could allow,” “may be appropriate,” “in select circumstances.” It’s real movement, yes—but wrapped in enough caveats to pad a liability waiver. For the first time, NAMs are stepping into the actual regulatory arena—not a white paper, not a webinar—but the fine print makes clear: the mice should stay packed, but not yet unpacked.

Yet the skepticism within FDA remains palpable: "The FDA has been accepting non-animal data since the Clinton years when it makes scientific sense," my insider source notes with an eye-roll that could power a small turbine. "This roadmap is more aspirational than a vision board at a life-coaching seminar. Divisions will still expect six-month monkey tox unless you bring knockout data, human MPS chips manufactured by wizards, and a target with zero cardiotoxic whispers from three galaxies away. Even then, they'll say 'maybe' while checking if you wore the right necktie."

The mice keep their U-Hauls idling at the curb, freedom delayed by the delta between press releases and scientific reality. One rodent applies an extra coat of mascara, just in case tomorrow brings more sacrifice for science.

Rainbow Draws – Populist Swagger vs. Deregulatory Zeal

And now the math that refuses the romance: Makary vows to ax 3,500 heads (approximately one-fifth of the agency), yet personally police every Red #40 fleck in Little Debbie cakes, every titanium dioxide particle in Skittles, and every synthetic strawberry molecule that's ever brushed against a kindergartner's taste buds. He brandishes head-count spreadsheets (9,500 in '06, 18,000+ today!) like they're cocktail napkin calculations rather than the result of twenty-plus congressional mandates, six pandemics, and a globalized supply chain that includes fly-by-night API factories in every province China hasn't yet mapped.

"Today, the FDA is asking food companies to substitute petrochemical dyes with natural ingredients for American children," Makary says in a press conference, a sentence that performs the syntactic equivalent of a Cirque du Soleil contortionist act—eliminating government oversight while simultaneously promising more aggressive regulatory action. It's the bureaucratic version of "this sentence is false," a paradoxical pretzel that would make Gödel reach for the Advil.

The RFK-ordered staffing cuts slashed project managers who coordinate complex oncology reviews, IT liaisons who maintain the electronic submission portal that prevents paper NDAs from reaching the ceiling, and interdepartmental coordinators who ensure that the cardio-renal division knows what the pulmonary division is doing when a heart-failure drug affects kidney function—the invisible infrastructure that keeps applications moving through the byzantine labyrinth of scientific review. Not "paper-pushers," but air-traffic controllers for molecules that might save lives or end them.

The result? Early signs of review gridlock appeared faster than mold on gas-station sushi. The dealer wants both the applause for clearing the table and credit for policing it more closely—a regulatory Schrödinger's cat that is simultaneously dead from budget cuts and more vigilant than ever. Before this all began: the Government Accountability Office (GAO-25-106775) flagged "investigator attrition" within the inspection arm of the agency, warning that this has resulted in “a large number of relatively inexperienced investigators". BioPharma Dive amplified a dire letter from AdvaMed CEO Scott Whitaker to HHS, urging reversal of the layoffs and calling them "a very negative impact on patient care." Even device makers—traditionally less FDA-dependent than pharma—were sounding five-alarm warnings.

The comedy-tragedy reached peak Ionesco when FDA had to quietly re-hire device reviewers it had just fired. One probably apocryphal manager texted me a GIF of a snake eating itself; I replied with the Ouroboros emoji, regulatory edition.

Twin Tells & The Defenestration of Marks

Shibboleth Shuffle

Seed oils. Microplastics. Beagle torture. "One-in-22 autism." "Half our kids are sick." Each phrase lands in Makary's Megyn Kelly love-fest like a casino comp—free, addictive, nutritionally void, and designed to keep you at the table long after mathematical reality suggests cashing out. These verbal shibboleths function as decoder rings for Makary's actual priorities, the password-phrases that separate the podcast-pilled from the normies.

Dig beneath the sound bites with the attention span of an actual scientist, and you find numbers that are technically traceable yet strategically maximized through statistical taxidermy: CDC's 4.5 percent autism rate in California children transmutes into "boys" (because boys sound scarier than "children") and then into "1 in 22" (because fractions feel more visceral than percentages). NIH's autoimmune baseline of 1 in 9 women inflates to a tidy 1 in 6 because advocacy papers permit the stretch, and rounded fear sells better than nuanced baselines. Prediabetes afflicts 1 in 5 adolescents according to JAMA Pediatrics—a concerning but precise figure that somehow transmogrifies into "half of all kids are sick" by the time it reaches Makary’s card-shuffling rhetoric.

Window Seat for Peter Marks

March 28th: Vaccine guru Peter Marks—the FDA's most respected scientist, the regulatory monk who brainchilded Operation Warp Speed and wanted to bring more of that urgent tempo to the rest of drug development—receives a "resign or be fired" ultimatum, and takes the hero’s exit by resigning with dignity intact. One week earlier, Makary had been sworn in with the publicity equivalent of a cone of silence; Politico reports he "initialed the order" personally, perhaps while practicing his poker face in the mirror.

The quiet coup sent tremors through the biologics and gene therapy divisions where Marks had earned nearly universal respect for his scientific rigor and political agnosticism—that rarest of Washington creatures, a genuine technocrat who could explain mRNA platforms to both Elizabeth Warren and Ted Cruz without either reaching for a sidearm. His defenestration—less resignation than high-rise window drop—set off alarm bells from Cambridge to South San Francisco. Cell therapy stocks that were already trading at post-pandemic lows slump lower within a week. The gene-therapy table tilts, chips slide south, and the house edge suddenly feels less like probability and more like destiny.

Biotech indices would drop 4% the day Marks' exit was confirmed—a market tell that spoke volumes about industry confidence in the new regime; the grownups have left the building, and the substitute teacher believes in crystal healing.

Wild‑Card Seat 5 – Vinay Prasad Arrives With Matches

May 6th: Makary deals a new player into the game—Twitter pugilist and medical iconoclast Vinay Prasad as director of CBER; this is the regulatory equivalent of appointing a fire marshal who collects vintage gasoline cans and sleeps with matches under his pillow.

Prasad—whose online oeuvre bespeaks a man willing to die on various epistemological hills with a kind of performative martyrdom that appeals to both the hyper-educated and the perpetually aggrieved—has publicly opposed adding Covid-19 shots to the childhood vaccination schedule and repeatedly blasted "drug approvals lacking rigorous evidence," which is roughly akin to complaining that Olympic diving judges aren't sufficiently attentive to splash size. His Substack reveals the sort of intellectual contrarianism that makes academic department heads reach for their Maalox: he's argued the NIH should "de-prioritize mRNA vaccine science for five years," calling the platform "oversold" despite its having saved roughly the population equivalent of Vermont, Wyoming, and both Dakotas combined.

What really animates Dr. P is his zero-tolerance financial ethics framework wherein any pharma adjacency—even a $12 bagel at a conference, one imagines—constitutes irredeemable "corruption". He employs meta-analyses like rhetorical hand grenades, citing population-level evidence that industry payments correlate with prescribing patterns while refusing to entertain the possibility that individual physicians might maintain their clinical autonomy despite once attending a Pfizer-sponsored dinner where the chicken was surprisingly decent.

Perhaps most telling is his notorious block-finger (a digital appendage that seems to twitch with the hyperactive sensitivity of those motion-activated Halloween decorations that startle you at CVS in September): he routinely exiles UCSF peers, FDA-adjacent founders, and anyone who questions his methodological parameters after a single critical thread—suggesting a regulatory style where dissenting voices might find themselves excommunicated faster than you can say "inadequately powered phase II trial."

Vaccine developers stare at their chip stacks and wonder if the game just switched to five‑card draw with Molotov rules. The wild card has entered the game, and he's not here to make friends.

When the Deck Slows – Deadline Slips, Data Blackouts, One Dupixent Spark

April 1st: No joke—FDA blows the Novavax COVID-19 vaccine PDUFA clock like it's made of spun sugar, then demands a brand-new efficacy trial with endpoints that would make a statistician develop a nervous tic. Daré Bioscience reports that feedback on their sildenafil cream (yes, viagra for vulvas—science is amazing) has slipped past two FDA deadlines, leaving their female arousal disorder trial in a state of, well, unaroused anticipation.

The National Drug Code directory—that essential database that tells hospitals which drug is in which vial at which concentration from which manufacturer—goes dark for two weeks because the IT liaison was among the 3,500 "non-essentials" eliminated in the purge. Pharmaceutical supply chain managers refresh browsers hourly, cursing in supply-chain-specific dialects that involve logistics jargon and creative parentage theories.

A rare disease startup called Stealth BioTherapeutics had spent nearly a decade coaxing its mitochondrial rescue drug, elamipretide, through the FDA’s labyrinth for Barth syndrome—a pediatric disease so rare it could hold patient meetups in a Starbucks. After two delays, one refusal-to-file letter, and a 10–6 positive advisory vote, the agency blew past the April 29 PDUFA date without explanation or rescheduling. “These delays are not connected to the recent reorganization,” insisted an HHS spokesperson, like a chatbot stuck in a legalese loop. Stealth, meanwhile, sits waiting, hopeful but helpless, caught between statistical orthodoxy, bureaucratic reshuffles, and 300 families anxiously watching their calendars run out.

Amid the bureaucratic haze, one faint light flickers through the regulatory fog: on April 18th, Dupixent (dupilumab) for chronic spontaneous urticaria—those nightmare hives that turn your skin into a topographical map of hell—squeaks through on schedule. The approval generates the surreal euphoria of finding an ATM that works in a Vegas casino at 3 a.m.: proof that the machinery still functions, if sporadically, and possibly only for drugs that already have six indications and fourteen years of safety data. A single ace showing in an otherwise bluffing hand, but enough to keep hope alive for the most optimistic pharma execs, the ones who still believe in both the Easter Bunny and the six-month PDUFA clock.

Dealer’s Tell – The Man Torn in Two

Makary isn't just dealing cards; he's dealing with the crushing weight of contradictory mandates. The man oscillates between surgical precision and populist performance art, trapped in a regulatory Kobayashi Maru where every option leads to someone's outrage. You catch glimpses of this—fleeting micro-expressions of authentic doubt crossing his face when RFK Jr. texts another supplement endorsement, a momentary flinch when an aide whispers about skyrocketing reviewer attrition rates. His pocket kings aren't just vulnerable; they're tearing him apart.

Makary is a man drowning in dual identities: Johns Hopkins surgeon with gold-standard technical skills versus podcast-circuit contrarian; evidence-driven clinician versus seed-oil paranoiac; regulatory steward versus deregulatory iconoclast. During a rare unguarded moment at a sparsely attended industry roundtable, he admits: “I'm trying to protect the core functions while satisfying certain... expectations.” The ellipsis hangs in the air like cigarette smoke in a bygone era, pregnant with the unspoken reality that his political masters demand both bureaucratic blood sacrifice and magical regulatory efficiency.

Late at night, while the Saloon’s cocktail waitresses maneuver between tables with the practiced precision FDA reviewers once applied to NDAs, you catch Makary staring into the middle distance, fingers absently riffling a deck of regulatory cards whose rules change daily. The man isn't evil; he's caught between the gravitational pull of scientific rigor and the event horizon of populist fury. His predicament isn't unique—it's the eternal struggle of the technocrat conscripted into ideological warfare, the expert weaponized against expertise itself.

You glance at your chip stack—investments in three Phase II assets, a preclinical platform, and a diagnostic AI that requires both FDA clearance and physician adoption to mean anything beyond PowerPoint promises at JP Morgan Healthcare Week. The felt suddenly feels like quicksand. Prasad quotes a Bayesian framework with the zealotry of a convert while simultaneously dismissing Bayesian methods for post-marketing surveillance. The hall-of-mirrors logic would be impressive if it weren't threatening to strangle the entire drug development ecosystem.

Final Hand – Table‑Flip

At 4:00 a.m., with Makary grinning behind the dealer tray and the RFK bobblehead still nodding in approval. Something inside you—call it the vestigial rage of every scientist who's ever had their methodology questioned by someone who couldn't pipette water without contaminating the sample—finally snaps.

Enough.

You stand, grip the cedar edge (solid, weighted, the kind of craftsmanship that costs $27,000 in federal contracting dollars and launches seventeen congressional investigations), and heave.

Felt flies, cards whirl like autumn leaves, stacks scatter into the neon void.

"I don't want to play anymore, Marty," you say, voice steady despite the chaos. The words emerge with the quiet finality of a Phase III trial stopped for futility. "Not at this table, not with these rules, not while the dealer keeps one hand on the deck and the other hitting refresh on RFK's Twitter feed."

The room freezes—cocktail waitress mid-pour, security guard mid-stride, Prasad mid-tweet about the methodological inadequacies of everything ever published in the New England Journal of Medicine.

"I don't trust a table where the house odds change mid-shoe, where the pit boss whispers seed-oil koans, where the drunk guy in seat 4 (RFK Jr.) keeps swapping the rulebook for a bumper-sticker and going all-in. This isn't regulation anymore; it's performance art with deadly stakes."

Makary's face—trapped between surgical mask and administrative gauntlet, between Johns Hopkins prestige and populist credibility—flickers with something that might be understanding. For one electric moment, the facade cracks, and you see the man behind the dealer button: exhausted, conflicted, trying to reconcile irreconcilable masters while keeping the regulatory lights on.

He shuffles the deck again, faster now, cards blurring like regulations in revision. Around him, the chip stacks are smaller, sadder. Janet Woodcock—who has outlasted ten commissioners and will likely outlast ten more—sips her herbal tea, quietly waiting for the pendulum to swing back and the lights to flicker on.

And this, maybe, is the final tell—not Makary’s poker face or Prasad’s Substack, but the deep, distinctly American fear that the game itself no longer runs on rules. That regulation has become a kind of interpretive dance: random, self-referential, and hostile to the very notion of knowable reality.

Not too strict. Not too lax. Just incoherent.

You don’t leave the table because you’re losing. You leave because you can’t tell if the dealer is following Hoyle or Goop.

And until the rules stop shifting beneath the felt—until science stops having to audition for its own job—some of us will be waiting at the rail. Arms crossed. Chips pocketed. Watching.