A landmark event in medicine was reported this week that has implications well beyond its likelihood of saving a baby’s life. Until now, commercially available CRISPR genome editing (Casgevy) was not capable of directly fixing a genomic defect. It was a workaround plan, that can be regarded as CRISPR 1.0. In this edition of Ground Truths, I’m going to take you through the advances in genome editing and why the new case report at NEJM heralds an extraordinary opportunity for the future of medicine.
A photo of K.J. Muldoon provided by the family,. He is now 9.5 months old
This is the type of genome editing that led to regulatory approvals for sickle cell disease and beta-thalassemia in late 2023, after a decade or research. It relies on making a double-strand break in DNA, as shown below, cutting it into 2 pieces. When that occurs the cell wants to repair the chromosome broken ends. But that leaves a small percentage of mistakes in the repair process of rejoining. The Cas 9 nuclease keeps cutting and more mistakes accumulate. Ultimately, the gene is disrupted when Cas9 can no longer recognize the mistake-laden sequence pf insertions and deletions. This is a disruptive knockout strategy that doesn’t fix a gene. That works for sickle cell disease and beta-thalassemia because the disruption targets a gene called BCL11A (that turns off fetal hemoglobin production) to restore fetal hemoglobin production instead of actually fixing the defect in the hemoglobin gene. The editing is done ex vivo—outside the patient’s body.
That lack of fixing also sets the stage for a very complicated treatment course. The individual has to undergo a collection process of blood-producing stem cells that requires being connected to an apharesis machine for several hours, getting multiple transfusions, then chemotherapy to wipe out the bone marrow. This leads to a precipitous drop in white blood cells and requires hospitalization for weeks or months, under sterile conditions. Ultimately, the edited blood stem cells are infused but the patients is stuck in the hospital until the immune system recovers. Sounds grueling, very expensive, and complicated? Yes, it sure is.
Moving Forward with CRISPR 2.0
Instead of a double-strand break, base editing (pioneered by David Liu and colleagues, and discussed in our podcast) creates a single-strand nick (Figure below from Wang et al) and sets up a precise single base pair substitution, such as changing A's into G's G's into A's T's into C's or C's into T's. This constitutes directly fixing of the defect by doing chemistry of an individual’s DNA base.
Base editors were used in the new report, as we’ll get into. They are great for certain single base pair substations, but not all. There is another methodology called prime editing that is more versatile, capable of changing an A to a T or insertions of multiple missing letters like CTT, the most common genomic basis for cystic fibrosis. It is regarded as CRISPR 3.0. For more depth on the different editors, this is a very good review paper in Cell.
This was unique in many respects. KJ Muldoon was born in August 2024 with lethargy, rigid muscles and other worrisome symptoms. Genome sequencing revealed this was due to a severe urea-cycle disorder that leads to accumulation of ammonia and death in about half of infants affected, and short of death, the high levels of ammonia cause lethargy, seizures, coma, and brain damage. The disease-causing gene was CPS1 (carbamoyl-phosphate synthetase 1 deficiency), a 1 in a 1.3 million births genetic (ultra-rare) disease. KJ was hospitalized and awaited a liver transplant, listed at 5 month of age, if a donor organ became available. In the meantime, therapy consisted of a low protein diet and ammonia lowering (“nitrogen scavenger”) medications.
To get to the basis of KJ’s genomic defect and attempt a cure, the team at Children’s Hospital of Philadelphia (CHOP) and Penn Medicine (led by Drs. Rebecca Ahrens-Nicklas and Kiran Musunuru) sequenced KJ and his parents. The father had a truncating CSP1 variant (Q335X) and the mother a different variant, E714X). They developed an adenosine base editor (called K-abe, schematic below) to specifically correct KJ’s defective CPS1 gene. The approach taken was particularly rigorous and comprehensive. Within 6 months they tested the editor in cells with the genomic variants, in mice (bred to specifically have KJ’s CPS1 mutation), in non-human primates, and got FDA approval to give it. It was administered intravenously using delivery via mRNA + nanoparticles beginning in February 2025 and then with 2 subsequent doses. The base editor used was directed against the paternal mutation (a G→A stop variant) at the Q335X site of the CSP1 gene.
Dosing started at ultra-low and the first showed little efficacy as reflected by plasma ammonia levels. The second dose was ~3 weeks later and the third dose (not reported in the NEJM paper) was in April, just ~2 weeks ago. These showed signs of clinical benefit (vida infra).
The compressed timeline for achieving all this work was unprecedented!
What is missing to date is a liver biopsy, due to risk to the infant, to prove the targeted CSP1 editing. There is also lacking evidence of a cure—”just” a reduced need for medications and the restrictive diet. But also encouraging is that KJ is now reaching developmental milestones and although he sustained two viral infections, both were without an ammonia crisis. Further doses of the base editor can be administered with the mRNA approach (rather than a virus vector that can induce an immune response). Regarding uncertainties, we also don’t know about the durability of the editing, any mosaicism impact (only some liver cells edited), and the potential of any off-target effects (rigorously assessed in the 6-months sprint of lab experiments but not yet in KJ).
This case of KJ represents a human first—-personalized, N-of-1 genomic intervention with base editing (CRISPR 2.0), in the body (in vivo), to directly fix a pathogenic (disease-causing) gene mutation. This bespoke intervention was accomplished in a remarkably compressed timeline that included rigorous assessment in cell and animal models, along with regulatory approval to proceed. It embodies something in medicine we have not and could not have done previously. It involved a dedicated team at CHOP and Penn and collaborators spread out around the world.
There are many specific aspects of the case that deserve attention. The fact that this work culminated from many years of NIH supported research, including the current report, at a time when we’re seeing profound and indiscriminate cutting of such funds
Related to that is the use of the mRNA-nanoparticle package for delivery of the intervention that is also being subject to cuts in funding at NIH without basis, no less potential lack of support by FDA, tied into misguided concerns about the Covid shots that saved the lives of over 30 million people. The mRNA delivery platform is also being used for developing vaccines for infectious pathogens for which there is no vaccine, for the genome editing programs, for cancer vaccines that have been successful for treating intractable cancers (neoantigen vaccines for both pancreatic cancer and renal cell carcinoma have been reported with a striking reponse in a limited number of patients).
We don’t know the actual cost of KJ’s genome editing, but had he gone onto a liver transplant it would likely have exceeded what this project cumulatively cost, and was supported by in kind contributions from multiple companies including Danaher, Aldevron Biosciences, Acuitas Therapeutics, and Integrated DNA Technologies.
The most important takeaway is that we have a new way of approaching rare disease with base and prime editors which account for ~90% of disease causing genetic mutations. Recall that there are about 10 thousand genetic rare diseases affecting ~6% of the world’s population, or about 400 million people. The overall global burden of rare and ultra-rare genetic diseases is huge, Were the approach pioneered in this case report made scalable, less expensive, and practical, imagine how many people could benefit.
Indeed, we are likely to see such scalability in the future. Many of the steps along the way here could be streamlined, some even omitted, such that this case be considered a template for the future. While today we can only approach diseases based in the liver, and potentially by intrathecal delivery into the brain, or outside the body editing T cells (or other cells), there is arduous work to improve the breadth of in vivo delivery to other vital organs. The Innovative Genomics Institute at UC Berkeley is orchestrating such streamlining efforts along with expanding targets to the lung, muscle and spine (the latter to achieve control of pain). Genomic editing in utero has also started.
There is another reason that this case is so important. Many rare diseases share common threads with common diseases. In my new book SUPER AGERS, which hit the NYT bestseller list this week, I explain how fixing the rare genetic defect of familial hypercholesterolemia with base editing, which is being undertaken by Verve Therapeutics, could be the basis of a one-shot treatment to prevent heart disease someday in the future. There is already preliminary work ongoing for prevention of Alzheimer’s disease with gene therapy of the APOE allele in people with two copies of APOE4, carrying a very high risk for the disease. And there are many other examples for how such advances for a rare disease could ultimately transform our approaches for important common diseases. It will take time, but I hope this post transmits the promise and excitement that lies ahead.
All content on Ground Truths— newsletters, analyses, and podcasts—is free, open-access.
Paid subscriptions are voluntary and all proceeds from them go to support Scripps Research. They do allow for posting comments and questions, which I do my best to respond to. Please don't hesitate to post comments and give me feedback. Many thanks to those who have contributed—they have greatly helped fund our summer internship programs for the past two years.
The scene in Kyiv earlier this month recalled the darkest days of oligarchic rule. U.S. Treasury Secretary Scott Bessent slipped a piece of paper across the table to Volodmyr Zelensky. “You really need to sign this,” Bessent told the Ukrainian president, according to The Wall Street Journal. The document was a deal to give the United States the rights to hundreds of billions of dollars’ worth of Ukraine’s minerals. When Zelensky said that he needed time to consider the proposal, Bessent pushed the paper closer to him and warned that “people back in Washington” would be very upset.
The Trump administration was operating in the old spirit of the kleptocrats who built fortunes in Ukraine and Russia at the dawn of the post-Communist era, wielding veiled threats to bully the nation’s leader into hastily handing over precious resources in a shady deal.
To Zelensky’s credit, he did his best to resist Bessent’s pressure. “I can’t sell our state,” he explained. It was as if he had actually internalized the message that American diplomats from the Bush, Obama, and Biden administrations had attempted to drum into Ukraine’s collective psyche: Ukraine’s democracy depends on it resisting powerful business interests that seek to plunder its wealth on terms highly unfavorable to the Ukrainian public. Zelensky’s willingness to stand up to President Donald Trump, holding true to American values in the face of American intimidation, was a perverse trading of places.
The moment recalls another episode in Ukraine’s recent past. Three years ago today, Russian troops streamed across the nation’s borders, assassins descended on the capital in search of its president, citizens decamped to the subways in search of shelter. Western intelligence agencies predicted Ukraine’s imminent demise. And in that moment of despair, Zelensky strode out into the empty streets of Kyiv, in the dark of night, to record a video reassuring the world, “We are still here.”
In those initial days of the war, Zelensky began to pose as a defender of liberalism, fighting on behalf of global democracy. Whether he actually meant it wasn’t clear. Before the war, his record of curbing corruption was spotty at best. With his political inexperience, and his strange unwillingness to prepare his country against the looming Russian threat, the former comic actor hardly had the makings of a sturdy bulwark against autocracy.
But he became one in the face of an unrelenting assault. Having preserved his nation’s independence, however, he’s now facing not one but two of the world’s most powerful illiberal leaders, conspiring in tandem. For reasons both petty and pecuniary, Trump seems intent on fulfilling Russian President Vladimir Putin’s goal of crushing Ukrainian sovereignty. The American president is pressing for Russia’s favored resolution to the war, without even allowing Zelensky a seat at the negotiating table. And the resource deal he’s pursuing amounts to World War I–style reparations, but extracted from the victim of aggression. It would force the Ukrainians to hand over the wealth beneath their ground, without any guarantee of their security in exchange. The extortion that Trump proposes would deny Ukraine any possibility of recovering economically, and consign its people to a state of servitude.
In this new moment of crisis, Zelensky is reverting to the role he played in the war’s earliest days. Confronted with blunt force, he’s bravely resisting. Squaring up to the bully, he accused Trump of swimming in disinformation. Despite all the pressure the United States has applied on him to accede to the mineral deal, he’s refused. Yesterday, he said, “I am not signing something that ten generations of Ukrainians will have to repay.” Knowing that Trump will never set aside his personal animosity toward him, he offered to resign in exchange for a Western security guarantee.
He has resisted the administration’s demands despite the fact that he has no leverage in his dealings with the U.S. other than moral suasion and a limited ability to get in Trump’s way. Ukraine’s military is entirely dependent on American arms, and its European allies can do almost nothing, at this late date, to fill the void. In the end, given Ukraine’s tenuous existence, Zelensky might have little choice but to accept whatever Trump imposes, but at least he’s shown that there’s a course other than immediate surrender.
Once upon a time, the United States poured diplomatic resources and military aid into Ukraine so that it wouldn’t descend into Russian-style autocracy. Now it’s the United States that’s headed in that direction. In the form of Elon Musk, an oligarch has captured the power of the American government, through which he can invisibly advance his own interests. The president is attempting to intimidate (and sue) the media into complying with the administration’s agenda. The norms of the administrative state have been shattered so that Trump can reward cronies and punish enemies. And in the most literal sense, the United States is collaborating with Russian autocracy so that the foreign policies of the two regimes are more closely aligned.
American institutions have largely faltered amid Trump’s assault, and European allies have aimlessly panicked. But Zelensky’s very presence reprimands the West for its futile opposition; his resoluteness shames Republicans, who once admired him as a latter-day Winston Churchill, for their own abject capitulation. Although he arguably has more to lose from a Trump administration than anyone on the planet, he’s kept pushing back, with resourcefulness that recalls Ukraine’s guerrilla tactics immediately after the Russian invasion. When the history of the era is written, Zelensky will be seen as the global leader of the anti-authoritarian resistance, who refused to accept the terms that the powerful sought to impose on his nation. He clarified the terms of the struggle with his heroic example. He reminds despairing liberals, “We are still here.”
The great American film-maker died this week, leaving behind a body of work unmatched in its seductive strangeness and transcendent mystery. We put it in order
It is one of life’s eternal mysteries that for the last two decades of his life, no one was willing to fund another feature by America’s greatest film-maker of the time. Almost as much of a mystery was his final completed feature: the evil twin of his previous film, Mulholland Drive. As Laura Dern’s hexed actor segues into the character she is playing, this digitally shot rampage down Hollywood’s boulevard of broken dreams dials up the narrative fragmentation of his late period. It runs the gamut from inspired camcorder surrealism to making-it-up-as-you-go-along incoherence (which is what it was: Lynch shot without a finished screenplay).
Sometimes it feels as if the only way to write about television is to write about business. As Peak TV recedes further and further into our rearview mirror, the conversation around the medium has increasingly focused on the way that the streaming TV model—and its Wall Street backers—have warped both the business and artistry of making TV shows. In the last year alone, we’ve talked about how Netflix has made early and premature cancellation an integral component of its business model. How Warner Bros. Discovery has been steadily hollowing out the once-storied HBO brand and filling it with Harry Potter. How streamers keep pumping out franchise tie-ins hoping to cash in on the success of movies like Dune and The Batman, which only end up feeling like homework. Just this week a major expose on Netflix’s business practices has got all my feed tittering about explicit instructions to screenwriters to write dialogue that anticipates an audience that has at least one eye on another activity.
All of this reportage is accurate and important, but to me it all feels like it’s circling around a single issue: timing. If I had to sum up the one thing that is consistently wrong with the majority of TV at the moment, the one way in which poisonous, short-sighted business practices are tearing down the accomplishments of the golden age of television, it would all come down to a poor understanding of timing. In 2024, and for some time before that, we were awash with examples how poor timing ruins what might have been a good, effective story. We’ve had shows that should have been a movie stretched out into six, eight, even ten hours. Shows that actually were a movie, twenty-five or thirty years ago, now compelled to come up with extraneous subplots and unnecessary complications to justify a format their story can’t sustain. Shows whose approach to this problem is merely to stall, taking an hour or more to reach what was once a perfect movie’s first act break. Shows that could have been a perfect network series, happily churning out twenty episodes a year, now reduced to eight or six. Shows that take a whole season to get to where their story should have started. Shows whose creators were informed, halfway into production, that they must cram several seasons’ worth of story into a handful of episodes. Shows that stretch out what should have been a 45-minute episode to something longer than an hour. Shows with no sense of what an episode is at all, that merely chop up a single narrative into a certain number of chapter. Shows returning after two or three years’ absence, fully expecting us to still remember—and be emotionally invested in—the events of their continuing story.
If there’s one trait common to all the shows I’m going to talk about in this post, it is that they have managed to buck this trend. These are shows whose creators are aware of the importance of timing in television storytelling. Shows whose episodes are their own units, capable of impacting the viewer in their own right, rather than just part of a whole. Show that respect the viewer’s time; that demand our attention and then reward us for giving it. Which is not, of course, to say that these shows exist separately from the business considerations that are currently shaping (in many cases, misshaping) TV. Two of them have already been cancelled. One is coming back for a second season, in what feels like an ill-considered, business-forward decision. One is a retelling of a popular movie. When it comes to the expensive, technically challenging business of making television, it’s never truly possible for art to rise above the economic landscape from which it emerges. But for whatever reason—talent, luck, sheer bloody-minded stubbornness—the artists who made these shows were able to hold their own just enough to make something special. Now more than ever, that feels worth celebrating.
Best Show of 2024:Shōgun (FX) and Interview With the Vampire (AMC)
For more than a decade, the entire TV field has been trying to make another Game of Thrones. This has translated into a myriad competing fantasy doorstopper adaptations, and a growing number of Game of Thrones spin-offs, none of which have managed to replicate that zeitgeist-capturing series’s magic. Now along comes a show with a truly questionable elevator pitch—a second adaptation of a dubiously-factual, blatantly orientalist novel that nobody reads anymore?—and reminds us that what made Game of Thrones a phenomenon wasn’t the magic or the dragons. It was the conversations. It was scene after scene of people with strong, interesting personalities lobbing loaded statements at one another, trading glances heavy with significance, playing chess with words, with war, conquest, and annihilation as the unspoken but ever-present stakes.
A surprisingly faithful adaptation of James Clavell’s novel that nevertheless reclaims it for the people it was actually about, Shōgun delivers exactly the things that made Game of Thrones so irresistible: the compelling characters, the high stakes, the subtle political maneuvering, the gorgeously realized setting. And yes, it’s full of people talking. Cosmo Jarvis’s John Blackthorne, at once a blowhard who can’t keep from imposing his worldview on a complex political situation that has nothing to do with him, and an intelligent, thoughtful man who slowly learns a new language and way of life. Anna Sawai’s Mariko, trapped by her gender and by her family’s role in Japan’s tumultuous succession games, playing the demure, obedient lady to the hilt, and nevertheless managing to cut her opponents to the bone. Tadanobu Asano’s Yabushige, scrambling desperately to appease multiple masters, slowly growing more comically philosophical as his options dwindle. Looming above them all, Hiroyuki Sanada’s Toranaga, who says little but directs all, whose ambition slowly and patiently reshapes his world. It’s through the conversations between these characters—and a vast and no less fascinating supporting cast—that Shōgun reminds us it is possible to tell a thrilling story of war and conquest without staging battle scenes with thousands of extras. That a simple tea ceremony can be as gutting as a beloved character committing seppuku. I am politely skeptical about FX’s ability to continue this show past the confines of Clavell’s novel, but having hit on the Game of Thrones formula so successfully, I can’t blame them for wanting to keep it going as long as they can—and am even cautiously excited.
Conversation is also at the heart of Interview With the Vampire, but whereas Shōgun‘s exchanges are subtle and full of unspoken meaning, in AMC’s adaptation of Anne Rice’s novel, they are overheated and melodramatic, played to the rafters—which is fitting for a show whose writing team boasts so many theater veterans, and whose second season is set in and around a grand guignol theater. Though the season’s events are violent and bloody—vampires Louis (Jacob Anderson) and Claudia (Delainey Hayles) flee the attempted murder of their master Lestat (Sam Reid) and find seeming safety with Armand (Assad Zaman) and his theater troupe, only for their new friends to turn on them, with tragic results—what the present-day framing story reveals that this show isn’t about vampirism so much as it is about marriage. As journalist Daniel (Eric Bogosian) interviews Louis about his life, what he’s actually doing is playing marriage counselor, revealing the abuses and manipulations of his two spouses, and the ways in which they all failed their daughter. The true violence in Interview With the Vampire isn’t the blood-sucking, limb-ripping-off kind. It’s Louis and Armand doing their best George and Martha impression, letting loose decades of frustration and resentment, throwing their most painful secrets at each other’s faces, and then coming back for a second round.
The result might have been trashy, soapy fun if it weren’t so sharply and impeccably written and acted. With a writing team stacked with die-hard Anne Rice fans who are nevertheless aware of the limitations of her work and its previous adaptations, Interview With the Vampireplays merry hell with levels of metafictionality, poking fun at itself while also reminding us that every narrative within it is someone’s story, with its own agenda and obscured elements. The entire cast knocks it out of the park—Reid leavening Lestat’s megalomania with just a hint of self-awareness; Hayles growing from an eternal child to a self-possessed woman; Zaman’s mask of wisdom and tranquility slipping to reveal gaping wounds; Bogosian’s world-weariness giving way to his youthful sense of wonder; most of all, Anderson’s pretense that the story he is telling is safely in the past shattering, revealing the rage and hurt that have never abated. Despite the difference in their tone, both Shōgun and Interview With the Vampire‘s success comes down the same thing—characters we care about, in the hands of writers who care about them, carrying on a conversation that we can’t get enough of.
Rest of the Best:
Baby Reindeer (Netflix)
Adapted from a successful Edinburgh Fringe show, Richard Gadd’s buzzy-yet-harrowing series still bears the hallmarks of a one-man show. It is told like a single, meandering narrative, relating to us, in a conversational, almost intimate way, how a failing comic (Gadd) becomes the obsession of a mentally ill woman (Jessica Gunning), and the how the process of dealing (and mostly failing to deal) with her stalking forces him to confront a past incident of rape and sexual abuse. So the first thing to praise about Baby Reindeer is how well it adapts its source material to a new format, not only expanding it and breaking it down into a coherent episodes (each of which packs a significant punch) but giving space to characters and perspectives outside of Gadd’s: Gunning, of course, whose Martha is at once monstrous, almost admirably intelligent, and deeply pitiable. But also Nava Mau as a trans woman Gadd falls in love with but can’t reveal his vulnerability to; Gerry Dunn as Gadd’s father, who haltingly tries to convey to him that he doesn’t think less of him for being raped; most of all, Tom Goodman-Hill as Gadd’s rapist, whose manipulations are terrifyingly plausible.
Beyond that achievement, however, I think what most strikes me about Baby Reindeer is what it reveals about how mass media tends to handle stories about sexual abuse. Gadd’s character is allowed to be an “imperfect” victim—of both his rapist and his stalker—in a way that women are almost never allowed to be. And on the other hand, being a man means that he can send out unmistakable signs of trauma, and specifically of having been raped, that remain completely illegible to everyone in his vicinity, even the people who love him, until he forces his way out from under a mountain of social expectations and actually says the unimaginable. As much as it is a deeply personal and idiosyncratic story, Baby Reindeer is also a commentary on how we process the issue of sexual violence, in fiction and real life.
Constellation (Apple TV+)
A somewhat qualified recommendation here, since Apple pulled the plug on this intriguing series when it was still only part-way through its story. Nevertheless, there’s much here to enjoy. Noomi Rapace plays an astronaut who returns to Earth after an accident only to discover that her life is subtly different: her husband acts distant; her colleague’s wife has the wrong name; her car is the wrong color. It’s easy, from that description, to guess what SFnal trope is being deployed, but Constellation plays things very close to the vest, forcing the audience to watch closely, untangling seeming contradictions—why is Jonathan Banks’s NASA scientist suddenly a washed-up ex-astronaut shilling his memoir on a cruise ship?—and working out for ourselves what’s going on. Contributing to this satisfying sense of disorientation is the fact that the show depicts Rapace’s predicament almost like a haunting, treating space exploration—and the specific situation that she finds herself in—like a supernatural occurrence. The result is atmospheric, but also thrilling and compelling, as Rapace not only realizes what’s happening to her, but forges bonds with people to whom she is really a stranger. It’s a great shame that Apple chose not to continue the show, but even what we got of it is extremely impressive.
Dead Boy Detectives (Netflix)
After American Gods, Good Omens, and The Sandman, it seemed like the time to admit that my reaction to adaptations of Neil Gaiman’s writing is roughly on par with my reaction to that writing itself—the materials of a great story always seem to be there, but somehow the execution results in something flat and uninvolving. I expected no better from Dead Boy Detectives, which adapts a Sandman story about two teenage ghosts who decide to forgo the afterlife in favor of solving mysteries on Earth, but instead I found something charming and vibrant. With only eight episodes on a format that might have once garnered fifteen or twenty, Dead Boy Detectives nevertheless instantly kicks into gear. Everything about it seems to work from the outset: the relationship between the two leads, fussy Edwardian schoolboy Edwin (Charles Rexstrew) and laid back 80s teen Charles (Jayden Revri), the quirky town fully of equally quirky characters they arrive in, the twisty, well-crafted mysteries of the week. Most of all, the unrequited romance between the two boys, which is handled sensitively and thoughtfully. Netflix unfortunately cancelled Dead Boy Detectives after only one season—either because of its by-now infamous unwillingness to let a show grow an audience, or because the revelations about Gaiman have made his name toxic—but the eight episodes we did get are an absolute delight.
Delicious in Dungeon (Netflix)
As someone for whom manga and anime are largely unknown quantities, I might have been expected to give this series, an adaptation of a bestselling manga by Ryoko Kui, a pass. If it weren’t for one thing: the premise, in which a troupe of D&D adventurers decide their best way to venture deep into a dungeon (and rescue a missing member of their party) is to capture and cook the monsters lurking within it, was utterly original and irresistible. The series’s handling of this premise is at once comedic—each episode is intercut with recipe cards informing you how you can make sorbet from ghosts, or how best to prepare dragon meat—and deadly serious. It treats the dungeon like an ecosystem, whose monsters function according to the logic of nature rather than the supernatural, each occupying their own ecological niche. And it gradually reveals the type of weirdos who would be willing to to try to unravel that ecosystem: a dwarf traumatized by the time he might have committed survival cannibalism; an autistic warrior who is utterly obsessed with monsters; a fussy magician who quickly reveals that no dark magic is beneath her; and an over-it, middle aged thief who just wants to get paid. The result is a wholly original fantasy story, gloriously realized with fantastic animation and voice work. In a year in which streaming TV always seemed to be converging on the lowest common denominator, this show—the product of a partnership between Netflix and heralded anime creators Studio Trigger—is a welcome example of originality, of trusting that if you put something new and different in front of them, audiences will respond.
Fantasmas (Max)
Hot on the heels of the cancelled-too-soon Los Espookys, and his movie Problemista, Julio Torres returns with yet another series that blends fantasy, comedy, surrealism, and deliberately chintzy-looking set design. In the show’s framing story, set in a quasi-futuristic New York, Torres plays a vaguely-defined creative (in one scene he consults on a new crayon color) who is rocked by the news that he must provide Proof of Existence to keep his apartment. Strenuously avoiding this bureaucratic necessity and its hidden emotional implications, he instead embarks on a quest to retrieve an oyster-shaped earring with which he can prove that his birthmark is getting bigger, and thus that he is dying of cancer. As convoluted and absurd as that story is, the bulk of Fantasmas is spent on individual sketches, stories that are told to Torres or which he stumbles upon, which often feature some major guest stars. Bowen Yang plays an elf who is suing Santa and Mrs. Claus for abusive labor practices. Emma Stone is a castmember on a Real Housewives-type show who realizes that she and the other women are being brainwashed. Steve Buscemi plays the letter Q in a Behind the Music-style documentary about how he overcame being one of the least-used letters of the alphabet. The result, like all of Torres’s work, is weird but expertly made, and like absolutely nothing else on TV.
Ludwig (BBC)
Is there a hole in your life where a quirky mystery show about an oddball, Sherlock Holmes-style detective could fit? Well, look no further than Ludwig, a show whose only flaw is that it’s from the BBC, so instead of getting twenty-two episodes, we have to content ourselves with six. David Mitchell plays John Taylor, a reclusive puzzle maker with social anxiety who is informed by his sister in law (Anna Maxwell Martin) that his twin brother James, a police detective, has gone missing. Naturally this leads to John taking James’s place and immediately beginning to solve murders through the use of logical deduction and puzzle-solving skills. This is, obviously, an absurd premise—as is the fact that the Cambridge police apparently encounter a large number of murders that can be reduced to a logic puzzle. That the whole thing works is down to Mitchell, who ably conveys John’s bewilderment at his new situation, his sharp intelligence, and the profound kindness and sense of justice that emerge as he pursues one murderer after another. And to the sharp mystery writing, which manages to take one specific type of murder mystery—a bunch of disparate characters with no apparent motive or means gathered together in a single location—and tell extremely varied and intriguing stories within that template. I promise, as soon as you finish Ludwig, you’ll be desperate for more of his adventures.
Mr. Loverman (BBC)
Based on the novel by Bernardine Evaristo, Mr. Loverman stars Lennie James as Barrington Walker, a septuagenarian Windrush generation immigrant who has built a successful life for himself in England—a thriving family, a successful business, the respect of his community. In a second, hidden life, however, Barry is a closeted gay man, who has for years carried an on-and-off affair with his best friend Morris (Ariyon Bakare). Now that his wife (Sharon D. Clarke) is at the end of her tether, Barry thinks he and Morris might be able to have a life together, but is taken aback when the latter starts asking for true openness. Evaristo’s novel was a master-class in marrying different tones, at once funny and tragic, clear-eyed about Barry’s flaws—his pride, his know-it-all bloviating, his indifference to the pain his lies have caused the people he loves—while also admiring his energy and determination, and recognizing just how difficult and dangerous life for gay men of his race and generation was. Adapted by Nathaniel Price, the show captures all these aspects of the story and character perfectly. You end up admiring and pitying Barry at the same time, feeling frustrated by his family’s inability to understand him, but also sad that they have been shut out of knowing who their father and grandfather really is. Most of all, you root for Barry and Morris, a sweet couple who have known and loved each other for too long for there to be any bullshit between them. Despite a light, often comedic touch, this was one of 2024’s most affecting and powerful shows.
Pachinko (Apple TV+)
Returning for a second season, this multigenerational, tear-jerking melodrama about a Korean family making their way in Japan from the 1930s to the 1980s remains as moving and impeccably-crafted as its first. This time around, the setting is WWII and the years following it, and though much attention has been paid to the depiction of the atomic bombing of Nagasaki—a short but shocking sequence—the real force of the show is in how it depicts day-to-day life throughout the war. Matriarch Sunja (Kim Min-ha) continues to come into her own as she struggles to keep her family fed and her growing sons on the right path. Her former lover Koh Hansu (Lee Min-ho) protects her but also can’t suppress his desire to possess her and her family. And as the years pass, the entire clan struggles with what their Korean-ness and Japanese-ness mean to them—when Sunja’s older son Noa (Kang Tae-Ju) goes to university, he is torn between acting the model Korean and joining the anti-government protests of Japanese students, and people in the periphery of the family debate whether to stay in Japan or join the revolution in Korea. The 80s storyline is a bit underpowered in contrast, but it does feature excellent performances from Youn Yuh-jung as the older Sunja, Jin Ha as her grandson Solomon, and Anna Sawai as the woman he falls in love with. Watching Pachinko is a reminder that sometimes the pinnacle of the television medium is just a meaty, well-acted soap opera, and as if that were not enough, the show still has the best opening credits on TV.
Ripley (Netflix)
Glorious as both an adaptation of Patricia Highsmith’s novel and a work of televisual artistry, this version of the story is faithful to a fault. It eschews the 1999 movie’s softer, gentler take on Tom Ripley, and here makes him something much closer to what he was in the novel: an almost reptilian conman and psychopath, consumed by a love of things, frustrated to the point of murder when his desire to insinuate himself into the world of privilege and luxury is frustrated. The show’s stunning black and white visuals, and its insistent soundtrack of clacking typewriter keys, voices wafting in from the street, and squelching flesh all serve to evoke emptiness—the emptiness of the world Ripley constructs for himself, and the emptiness of his own soul. But neither is this a show made up merely of beautiful vistas. Several stunning set-pieces convey the work—the intelligence, the physical effort, the sheer bloody-mindedness—that go into Ripley achieving his goals, whether that’s faking a correspondence or hiding a body. And it all moves at an absolutely perfect pace, neither rushing the novel’s events, nor slacking the tension we feel as Ripley is once again very nearly caught, or as someone who doesn’t entirely deserve it is nearly consumed by him. Like the movie, this adaptation misses some aspects of the novel—as I wrote earlier this year, its Ripley is too chilly to feel the sexual passion that the novel’s version suppresses, and that the movie’s gives way to—but to my mind it’s as close to perfect as we’ve ever gotten.
Wolf Hall: The Mirror and the Light (BBC)
Nine years after the miniseries adaptation of Hilary Mantel’s Wolf Hall and Bring Up the Bodies first aired, four years after the concluding volume in the trilogy, The Mirror & the Light, was published, and two years after Mantel’s death, the BBC finally concludes its adaptation of the Thomas Cromwell trilogy. As I wrote when the book was published, this is a conclusion that is at once essential—you can’t have a rise without a fall—and unnecessary, its seeds not just sown, but fully present, in the story’s previous installments. The miniseries, perhaps more affected than Mantel was by contemporary politics, changes the story’s emphasis in subtle but notable ways. It is less focused on Cromwell’s interiority, more interested in the challenges of navigating an increasingly querulous, narcissistic king and his self-absorbed, short-sighted courtiers. If this version of Cromwell starts to think of himself as a shadow king, the only person who can keep the country on an even keel and the heads of the royal family on their royal necks—well, the show seems to be asking, can you really blame him? The result is more tolerant of Cromwell than the already-quite-tolerant books, more inclined to take his side when he is shocked, shocked to discover that people are terrified of him. But, like the books, it is also a deeply human, and humanizing, portrait, of a man who despite all his power is still, in the end, just a man. If some of the magic of Mantel’s language is missing, it is more than made up for by Mark Rylance, Damian Lewis, and the fantastic cast around them. However belated, The Mirror and the Light is an excellent capstone on Mantel’s Cromwell project—which, sadly, has ended up being her life’s defining work.
Honorable Mentions:
Black Doves (Netflix) – What if The Big Chill was about assassins? That is the question this delightful confection of a spy series seeks to ask, and to which the answer turns out to be: it’ll be a lot of violent fun. Keira Knightely and Ben Whishaw play dysfunctional best friends trying to figure out why someone has killed Knightley’s lover and endangered her cover, along the way spreading chaos throughout London, and dealing with decades’ worth of emotional backlog, while wearing fantastic outfits and encountering a wide array of quirky characters played by fantastic actors. What more could you possibly want?
Expats (Amazon) – Nicole Kidman starring in a glossy adaptation of a bestselling work of women’s fiction has practically become a cliché, so it’s not surprising that Expats has flown a bit under the radar. But despite its schlocky description—Kidman is the wife of a businessman living in Hong Kong whose young son disappears—Expats is thoughtful and quietly harrowing. Gorgeously directed by Lulu Wang, its true focus is the city itself, from the enclaves of the rich where Kidman and her fellow rich Westerners gather, to the unseen world where their foreign nannies and maids spend their days off, to the burgeoning protest movement. It is at once a love letter to the city, and an indictment of its power to consume the innocent.
Mr. & Mrs. Smith (Amazon) – There probably isn’t a more dispiriting TV show pitch than “what if we made that Brad Pitt/Angelina Jolie movie from twenty years ago, that was fully coasting on their star power and the barest hint of a premise, into a TV show?” Happily, Amazon gave that project to Donald Glover, and he not only came up with some entertaining ideas about how the whole “married spies” concept works, but turned it into a sharp meditation about marriage and how it functions in the mundane day-to-day—even when that mundanity includes chasing assassins at an Italian ski resort. Glover and Maya Erskine aren’t instantly smooshable, but they’re each compelling in their own right, and by the time the season ends their relationship feels real and worth rooting—and killing—for.
Most Redeemed Genre of 2024 (Second Year Running): Mystery and Crime
I said this already last year, but something is happening that I can only call the Knives Out effect. TV producers have suddenly remembered how versatile and effective the mystery format is, and how well the constraints of the streaming era suit it—building a season of television around a single mystery gives you both a week-by-week hook, and a reason to bring audiences back for another story that won’t make them angry if it takes you two years to do so. As in 2023, we are reaping the results of this lightbulb moment. Only Murders in the Building—a show that started off fine and has just been getting better and better—returned for a delightful fourth season. Fargo and True Detective both made triumphant returns to form, suddenly reenergized after less-than-stellar efforts in the pre-Knives Out era. And a whole raft of new shows have got us rooting for a bunch of new detectives: Monsieur Spade, in which Clive Owen gives a career-best turn as an older Sam Spade, now a retired widower in the south of France, investigating a case that touches on the lingering trauma of the Nazi occupation and the Algerian war. Bad Monkey, a rollicking Carl Hiaasen adaptation, in which Vince Vaughan plays a motormouth detective unraveling a case that takes him from the Florida keys to the Bahamas. Get Millie Black, from Booker-winner Marlon James, about a troubled female detective who leaves London for Jamaica. And sure, there have been some duds this year too: Death and Other Details, which tried to imitate Knives Out point for point, only to fall flat on its face; Emperor of Ocean Park, which wasted an excellent cast on a plodding, padded story; The Day of the Jackal, which was fun most of the way through until suddenly turning into Dexter in its final episode. But even the failures are a testament to how well this genre works for the kind of TV we have these days. For all the complaints we rightly have about the state of the medium, this is a rare bright spot.
Best Show Unfortunately Adapted From a Literary Masterpiece:The Sympathizer (HBO)
Viet Thanh Nguyen’s Pulitzer-winning 2015 novel sits squarely among the great literature of the 21st century. A twisty, time-jumping portrait of a man who has tied himself into knots of conflicting loyalties and relative morality, who is on so many different sides that he no longer knows what right and wrong are, and who gives us a front row seat to Vietnam War and its aftermath that leaves us no less confused than he is over who and what we should be rooting for. HBO’s miniseries adaptation captures quite a lot of this. With direction by the likes of Park Chan-wook and Fernando Meirelles, adapted by Park and Don McKellar, it is a slick, gorgeously-realized affair that instantly conveys its settings—Saigon near the end of the war; California in the 70s; the set of a movie that is not, but actually is, Apocalypse Now—and carries you confidently from one to the other. Newcomer Hoa Xuande ably shoulders the seemingly impossible task of conveying the protagonist’s internal struggle and fracturing identity, and although the decision to have producer Robert Downey Jr. play all the story’s important white characters—a professor who boasts about his unique understanding of “the Oriental mind”; a warmongering congressman; a self-absorbed visionary director—has proved a bit of a double-edged sword (Downey was alone among the show’s mostly-Asian cast to receive award recognition), it is certainly true to how the novel sees these characters. But in the end, all you get is a seven hour version of the story you could have gotten from the book—and maybe a little less powerful in that story’s climax. There have been other flawed adaptations of great novels this year—My Brilliant Friend‘s final season was annoying, but then so was the book it’s based on; Netflix’s One Hundred Years of Solitude is far better than such an absurd-sounding project has any business being, but still can’t capture what actually makes the book work. The Sympathizer is, I believe, the only instance of a show that is genuinely great, but which ends up feeling kind of superfluous, simply because the novel it’s based on exists.
Show That Did What It Wanted to Do, Dammit, Even if it Maybe Shouldn’t Have:The Bear (FX)
The second season of The Bear was nearly a perfect work of television, expertly deploying the “let’s put on a show” format, marrying it to the current fascination with food and professional kitchens, and throwing a brilliant cast and great set of characters into the mix. The third season still has a lot of the ingredients that made the second one great, but it uses them to very different effect. It asks: what happens after you’ve put on the show? The answer turns out to be that you have to put it on again and again, every night for perhaps the rest of your life. “Every second counts”, the characters repeated to each other in the second season as a sort of life-affirming mantra, a reminder that their craft demands constant attention to detail and a relentless drive towards self-improvement. In the third season, this becomes a curse, as we realize how quickly weeks, months, even years can slip away while you’re paying attention to those seconds. Which might all have been fine, but the most impactful choice The Bear makes in its third season is to place the audience in the same headspace as its characters, caught in a stressful, unsatisfying stasis, waiting for Carmy and Richie to make up after their fight, for Carmy to apologize to Claire for how he treated her, for Syd to decide whether she wants to stay at the Bear or move on, for the goddamned Chicago Tribune review to drop. All of this, interspersed with increasingly unfunny Fak brothers comedy antics, and some standalone episodes that, while strong, aren’t a patch on last season’s similar entries. It’s obvious what Christopher Storer was going for in this season, but I can’t be alone in hoping that he’s gotten it out of his system, and will now be able to move forward with the story.
Show That Thinks it’s Decrying Misogyny While Actually Wallowing In It:Disclaimer (Apple TV+)
Alfonso Cuarón’s foray into prestige TV starts out in an enjoyable wrongfooting way. It presents us with three storylines—a documentary filmmaker who receives a novel in the mail that seems to be based on an incident from her past; a teenager vacationing in Italy who meets an alluring older woman; and a widower who discovers some photographs, and a manuscript, in his late wife’s things that seem to shed a new light on the death of their son—and not only starts to tie them together, but asks us to ponder where “fiction” and “reality” begin and end. It quickly becomes clear that the filmmaker (Cate Blanchett) is the woman the teenager becomes involved with, and that the widower (Kevin Kline) is the one who published and sent her the novel, but does that mean the Italy segments represent unvarnished reality, or fiction-within-fiction? It’s interesting enough to contemplate these questions that it actually takes a moment to realize that no one within the show is asking them. That as soon as Kline sends Blanchett’s colleagues and family copies of his novel, they all assume that it is telling a true story, and that Blanchett is a seducer and possibly a murderer. And then you notice that you have no way of working out whether this is true or not, because Blanchett’s character appears to have no interiority. Despite being an accomplished professional, she appears to have no emotional or intellectual resources to draw on, no means of expressing her own point of view. So determined is the show to paint her in the most flattening, misogynistic light, as a woman who has not only lied for decades, but who lacks the moral fibre to confront the people she’s hurt or face up to the things she’s done, that you start expecting the other show to drop. And when it does, it’s as clomping as the rest of the show, instantly taking Blanchett from evil temptress to innocent (spoilers, but I think you probably know where this is going) rape victim. And at no point passing through actual, complex human being. Disclaimer clearly thinks of itself as a trenchant commentary on how easily we believe the worst about women, perhaps even implicating its audience in that tendency. When really, what’s worthy of condemnation here is the shallow writing.
Show That Best Illustrates That Hollywood Can’t Satirize Itself:The Franchise (HBO)
At some point in the last decade, Hollywood writers seem to have become convinced that satire requires nothing more than putting something that happens in real life in your story, and having characters comment snidely about it. Readers, I am here to tell you that it takes a bit more than that. Case in point: The Franchise, which takes us behind the scenes of a grade-Z comics adaptation that is part of a mega-successful (but increasingly wobbly) superhero franchise. If you’ve been reading Deadline or Variety about the increasingly dysfunctional production process of these types of movies, you’ll recognize a lot of what happens in this show: the scripts that are rewritten on the spot because another corner of the franchise has been tweaked; the product placement parachuted in even when it makes no sense in the story; the female character who suddenly needs more lines because the studio is getting called out via hashtag. The problem isn’t simply that none of this is funny; it’s that none of it is even particularly trenchant. Beyond replicating reality in fiction, it has nothing to say. Which is only exacerbated by the fact that The Franchise never quite seems to know what the target of its satire actually is: is it Hollywood in general (in which case its focus on long-suffering below the line crewmembers, who have to be on call to realize the director’s latest whims or the studio’s latest dictates, makes more sense) or superhero franchises in particular (in which case the focus on these characters seems misguided—I find it hard to believe, and The Franchise never successfully argues, that the set of the latest Ant-Man movie is inherently more chaotic or abusive than that of John Wick or Megalopolis)? In fact, it’s precisely in the moments when it comes closest to hitting a real sore spot—such as the increasingly suicidal desperation of the film’s overworked VFX supervisor—that The Franchise seems to back off and retreat into ha-ha comedy, as if to remind us that anything genuinely ugly about Hollywood is off-limits. By the end of the season, it’s hard to understand what point this show thinks it’s making, and who it is even for.
Log in
