A new virus emerges in rural China. Although those who contract it initially display moderate, flu-like symptoms, their health quickly declines. The mortality rate is unclear, but one aspect is immediately obvious—it’s very contagious. Within three months, nations around the world are planning lockdown protocols and quarantine measures. Politicians seem completely out of their league and ill-equipped. 

The world eventually recovers from the ordeal, but consequences of the virus linger for decades.While society pushes forward, there’s no promise that an even deadlier virus isn’t already lurking out of sight.

This isn’t about COVID-19, by the way. It’s the plot to the novel World War Z—arguably the most realistic depiction of a zombie apocalypse ever created. Released 20 years ago this week, the horror novel by Max Brooks quickly became one of the undisputed cornerstones of walking dead canon. Readers and critics devoured the book (no pun intended), but their responses often worry Brooks. Much like the reception to his first book, The Zombie Survival Guide, many fans seem to misunderstand his intentions. These projects weren’t simply intended to entertain. Max Brooks was trying to warn everyone about the looming threats we would prefer to ignore.

While the 54-year-old writer ostensibly writes books about zombies, Sasquatch, and (soon) an alien invasion, his attention to disaster details and hyperrealism has earned him a parallel career as a security and threat analyst for some of the world’s most respected geopolitical think tanks.

To celebrate World War Z’s 20th anniversary, Popular Science recently spoke with Brooks about the book’s massive impact.

This interview has been edited for length and clarity.

Andrew Paul: Did you anticipate World War Z attaining the legacy it now has in popular culture?

Max Brooks: Oh, God no. Of course not. Especially because I’m never tapped into pop culture. I don’t know what anybody else is doing—even when it was my job writing for Saturday Night Live! I’m good at thinking about what I think about.

AP: Before World War Z, you wrote an actual preparedness handbook called The Zombie Survival Guide. What prompted you to take a hyperreal approach to such a seemingly outlandish subject?

MB: The reason I wrote [them] was because all the zombie stories, even to this day, tend to focus around small groups. To me, it’s like trying to understand World War II from watching Saving Private Ryan. I had big picture questions nobody was answering.

I think the best zombie movie ever made was Dawn of the Dead. To me, the most interesting part was when they’re holed up in the mall watching the news. That window into the wider world was so fascinating, and I wanted more.

AP: But there was a time when World War Z almost never happened, right?

MB: [The publisher] didn’t know what to do with The Zombie Survival Guide. Their marketing strategy almost killed my career before it even launched. They thought, “Well, no one is clearly that much of a loser that he’s actually spent this much time thinking about [zombies]. Clearly, he’s a cool guy making fun of those losers. And because he’s Mel Brooks’ son and he’s coming off SNL, we’re gonna position him as Mel Brooks, Jr. writing Younger Frankenstein.”

But The Zombie Survival Guide really is a disaster preparedness manual. It’s why [soldiers] took it to Afghanistan; people told me it saved their lives when they were lost in the woods. I didn’t make anything up. It’s not Hollywood stuff—it’s all about dehydration and dry socks and shelter.

But [these books were] legitimately the product of years of thinking, “If I was in a zombie world, how would I survive?” It really set me on this path of asking, “What happens when the grown-ups drop the ball?”

AP: And now it’s your job to worry professionally.

MB: I’ve now been part of three military and national security think tanks—the Atlantic Council, the Center for Strategic and International Studies, and the Modern War Institute at West Point. I’m a non-resident senior fellow at all three of them, and it’s my job to study real threats.

For some reason, I was not blessed with the wall of denial. Like, I can’t just say, “That would never happen and I’m just going to go about my merry way.” I’m already terrified! And the way to reduce my anxiety is to study the threat so that it’s not nebulous.

AP: What was the most difficult part in preparing to write World War Z?

MB: You don’t know what you don’t know, so you don’t know what you’re missing. There’s always a fear of groping around in the dark; of not even knowing who to talk to. That was a real struggle, because I’m an insular guy. I’m not a social guy. Part of it was talking to experts, but part of it was reading books—and I’m fully dyslexic. So that was a real slog.

It was also about never trusting the internet. I used it once or twice, like, to research laser weaponry. I literally went to a company’s website, saw their demonstration video, and was like, “Yeah, okay. That is not a practical weapon for hunting zombies. I see how long it takes to burn through something.”

AP: Obviously humanity’s most terrifying challenge in the last 20 years was the COVID-19 pandemic. How do you view that real-world horror in the context of World War Z? 

MB: COVID was scary because I knew it was coming thanks to my friends in the military and biodefense community. I was part of what was called the Blue Ribbon Biodefense Panel for germ attacks way before COVID. So I already had at my fingertips the ability to tell the difference between panic porn in the media and the real deal. I also had to study diseases enough to write about a zombie plague. But also, it came from being on the receiving end of a bioterror attack. When I worked at SNL [from 2001 to 2003], we had the anthrax letters delivered to our building [in October 2001].

So, I knew this was coming, but the question was how to warn people. I had people laughing at me. Ironically, the people who are the worst minds to reach are the smarty-smarts because they think they know everything.

AP: Were you expecting COVID to be much worse than it was?

MB: Oh, much worse. It got me into trouble, because I was prepping for, like, tanks on the street, you know? I was ready for that. I stocked my home with food that would last the longest as opposed to food that my wife would actually eat. 

But the irony is, had it been worse, we might have actually done better. Studying diseases over the years—it’s sort of like the slow zombie versus the fast zombie. The fast zombie is so scary you have to react. The slow zombie gives you the false sense of security. Like, “Oh, I can take ‘em out.” COVID was the slow zombie. It allowed us to be arrogant and dismiss it: “Oh, it’s no worse than the flu.”

AP: How did you see that play out during the quarantine?

MB: It goes back to when COVID hit New York City. I had written a book called The Harlem Hellfighters, which was a true story of African American soldiers in World War I. They’re still an active unit in the National Guard, and I’m friends with their chief medical officer. Their job was to pick up the dead bodies around New York.

He said to me, “If those bodies had been stacked up on the street for everyone to see them, there would have been no argument about masking or distancing or taking the vaccine.” The hiding of it is what allowed naysayers to get way more people killed.

AP: Where did the grown-ups “drop the ball,” as you say?

MB: I think the greatest failure on the part of leadership at every level was not publicizing the dead. Maybe they were afraid of angry letters and backlash and didn’t want to cause a panic, but that’s exactly what they should have done.

A doctor in Los Angeles told me they converted hospital rooms into morgues. He said, “You don’t believe the amount of bodies. We’ve got pyramids of body bags.” And I’m like, “Well, then why is this not on the news every night?”

AP: After experiencing an actual global plague, how do you feel about World War Z’s overall accuracy?

MB: I think it was accurate for the time. I would still have the plague coming from China, 100 percent. I would love to say that was my genius futuristic prediction, but no. I based it on SARS. And this is why it’s unforgivable that it happened again. If I wrote it today, I would really highlight why it was allowed to be [downplayed]—and the reason is our greed. All of our stuff is made in China.

I would also really change the politicization of information. We’re living in a time where all facts have become tribalized. We’ve had 20 years of such dumbing down that I think it would be a central tenant of the book.

AP: Would you change how the United States responded to a zombie outbreak?

MB: I still firmly believe we are a moderate country, but I don’t know how brave we are. In order for a crime to be committed, you don’t need 100 bullies. You just need one bully and 99 cowards.

The psycho fanatics have a microphone now, which was inconceivable 20 years ago. They are hate merchants, and the erosion of our education system has created a demand that the merchants supply.

AP: So you think we would have handled COVID differently in 2006?

MB: If COVID happened 20 years earlier, we would all have gotten vaccinated, because of all the grandmas and grandpas who grew up before the polio vaccine.

AP: What else has changed?

MB: When I talk to people in power, I try to educate them about what I call “uphill influence” versus “downhill influence.” Downhill influence is when there’s a pre-existing bias that you just need to hijack and ride downhill. There’s gravity already there, and that’s not necessarily a bad thing. It was an established fact 20 or 30 years ago that vaccines kept you safe. So, if you were rolling out a vaccine, you could already just ride that existence acceptance downhill. The gravity was with you.

Uphill is when you have to educate before you can even start to persuade. You first have to educate people about just the world that you’re trying to explain. Vaccines have gone from downhill to uphill. The [subjects] we all had to try to stay awake through in seventh grade science class aren’t even there anymore.

I understand [MAHA supporters] want a clean planet, food, and water, and all of that will make you healthier. However, in 1491, the people who lived on this continent had all that, right? The moment the first Javier Bardem-looking Spaniard coughed on them, whole civilizations died.

AP: Both of your zombie books hinge on public education, and that’s now a major aspect of your threat analysis work. Do you know why you keep returning to this theme?

MB: I think one of the reasons I’m so obsessed with education is because I was not a good student. I have such ferocious learning disabilities. I never felt instantly comfortable learning, and I’ve always had to find workarounds. My mother had to help me find workarounds so I could learn. So when I research, it takes so much time and effort and [there’s] so much insecurity. I understand how hard it is to teach something to someone who doesn’t naturally pick it up.

I’m very lucky that I come from two parents who had no formal education, but were both very smart. Most importantly, they were very curious. I became very comfortable with the idea of approaching something as an absolute beginner.

AP: It took 14 years between World War Z and your follow-up sci-fi novel, Devolution. Your next book, The First Hundred Hours: A Story of Alien Invasion, comes out in 2027. Is there a reason for such long pauses between these projects?

MB: I’m not a natural scientist. The amount I’ve had to study for this new book has been excruciating. But it’s very humbling having to talk to the experts and say things like, “Please talk to me like I’m a third grader—and not a smart third grader.”

AP: Would you end World War Z the same if it was set in 2026?

MB: I would still end it on a positive note, and I think that has to do with being an American. We don’t have the luxury of abandoning our ideals, because that’s all we are. We’re not a nation-state—the ideals in America are all that hold this mutt [of a] nation together. We all come from different places and tribes, and we all agree to live under a certain set of guidelines. It’s really critical that we fight for those guidelines.

If there is one takeaway, it’s the central reason I wrote the book in the first place. We’re all stuck on the same planet together, and that planet is not that big anymore. What affects some of us could potentially affect all of us. I think America has some amazing cultural strengths, but one of our weaknesses is our isolationism. That’s built on an outdated notion that we are somehow protected by two oceans and our geography. That’s not true anymore.

The post Max Brooks reflects on 20 years of ‘World War Z’ appeared first on Popular Science.

Endometriosis, a chronic inflammatory condition affecting an estimated one in ten women of reproductive age, has long frustrated clinicians with its stubborn tendency to recur despite surgery and hormone therapy. A new review published in Reproductive Sciences argues that the answer to this therapeutic failure may lie in a single transcription factor: ZEB1, or Zinc Finger E-Box Binding Homeobox 1. Written by Gaurav Doshi and Sanket Shirodkar of SVKM’s Dr. Bhanuben Nanavati College of Pharmacy in Mumbai, the review synthesises evidence from across the field to position ZEB1 as a master molecular integrator—converging hormonal, inflammatory and epigenetic signals into a single programme that drives lesion establishment, invasiveness and drug resistance.

The biological centrepiece of the review is epithelial–mesenchymal transition, or EMT, the process by which epithelial cells lose their adhesive, stationary character and acquire the migratory, invasive traits of mesenchymal cells. In endometriosis, EMT is thought to be essential for the survival of endometrial cells that reflux into the pelvic cavity during menstruation and subsequently implant on peritoneal surfaces, ovaries and other ectopic sites. ZEB1 sits at the apex of this programme. It suppresses CDH1, the gene encoding E-cadherin, the principal adhesion molecule holding epithelial sheets together, and in doing so dismantles the cell–cell junctions that would otherwise keep ectopic cells anchored and vulnerable. The review details how ZEB1 accomplishes this repression by recruiting chromatin-remodelling machinery, notably the SWI/SNF ATPase subunit BRG1, to the E-cadherin promoter, effectively silencing it epigenetically. The result is a stabilised mesenchymal differentiation that permits attachment, invasion and, ultimately, the vascularisation required for a lesion to persist.

Crucially, the authors argue that ZEB1 is not merely one EMT factor among many, such as SNAI1, SNAI2 or its paralog ZEB2, but a systems-level hub. Immunohistochemical and molecular studies have repeatedly shown selective upregulation of ZEB1 in ectopic endometriotic lesions compared with matched eutopic endometrium, and its expression is particularly pronounced in deep infiltrating disease. One frequently cited clinical study found ZEB1 expression to be a potential indicator of invasive endometriosis, while a pilot investigation of different disease phenotypes has extended these observations across superficial, ovarian and deep infiltrating subtypes. Measurable ZEB levels have even been detected in plasma and peritoneal fluid of patients with endometriosis and infertility, raising the prospect of ZEB-family proteins as circulating biomarkers.

Perhaps the most consequential section of the review concerns the bidirectional crosstalk between ZEB1 and sex steroid signalling. Endometriosis is a hormone-dependent disease, and its defining therapeutic problem is progesterone resistance: lesions fail to respond to the progestational drugs used to suppress them. The review marshals evidence that oestrogen, specifically 17β-estradiol, induces ZEB1 expression, and that ZEB1 in turn suppresses progesterone receptor pathways. This creates a self-reinforcing circuit in which the oestrogen-ZEB1 axis dismantles the molecular machinery that progesterone therapy depends upon. Experimental work has demonstrated that high ZEB1 expression accompanies 17β-estradiol-induced EMT in endometriotic cells, and parallel findings from other hormone-driven diseases reinforce the mechanism: in breast cancer, ZEB1 induces oestrogen receptor-α promoter hypermethylation and confers antiestrogen resistance, and ZEB-family members have been shown to regulate endocrine therapy sensitivity through both canonical and non-canonical routes. In endometriosis, EMT itself has been shown to contribute to the downregulation of progesterone receptor expression in lesions, and the near-uniform loss of progesterone receptor isoform B in ectopic tissue is a long-standing observation that the ZEB1 framework now helps to explain mechanistically.

The review also devotes substantial attention to the non-coding RNA dimension of ZEB1 regulation, describing a multilayered feedback architecture that locks the mesenchymal state in place. The miR-200 family of microRNAs normally targets the 3′ untranslated regions of ZEB1 and ZEB2 transcripts, holding EMT in check. In ectopic lesions, this double-negative feedback loop is subverted: ZEB1 represses miR-200 transcription, and the resulting loss of miR-200 pressure allows ZEB1 protein to accumulate. Long non-coding RNAs add another tier. The lncRNA AFAP1-AS1, for example, promotes EMT in endometriosis in a ZEB1-correlated manner, and the metastasis-associated transcript MALAT1 has been implicated in the same circuitry, with miR-200c suppressing endometriotic progression in vitro and in vivo by targeting it. Circular RNAs complete the picture. The circRNA circZFPM2 has been shown to promote EMT by sponging miR-205-5p and thereby releasing ZEB1 from repression, while hsa_circ_0063526 acts through the miR-141-5p/EMT axis and circATRNL1 acts upstream by upregulating the EMT cofactor YAP1. Together these competing endogenous RNA networks—a concept also validated in metastatic cancer by J Clin Invest work—build a ceRNA web that perpetuates ZEB1 expression long after the initial pro-EMT stimulus has passed.

The authors then connect ZEB1 to the two great downstream consequences of endometriotic lesions: chronic inflammation and fibrosis. Through interactions with the TGF-β pathway—upstream signals such as TGF-β1 activate SMAD2/3, which cooperate with ZEB1 to drive the mesenchymal programme—ZEB1-linked cells reshape the lesion microenvironment. Fibroblast-to-myofibroblast transdifferentiation, marked by α-smooth muscle actin expression, generates the dense extracellular matrix characteristic of endometriotic implants, and analogous MRTF-A–ZEB1–IRF9 axes have been documented in renal fibrosis. Inflammation completes the loop: pro-inflammatory cytokines such as TNF-α, IL-6 and IL-10, and peritoneal fluid cytokine profiles that differ across endometriosis subphenotypes, feed back into EMT signalling through MAPK, ERK, PI3K/AKT and NF-κB pathways, while immune evasion mechanisms—including indoleamine 2,3-dioxygenase-mediated suppression of natural killer cell cytotoxicity—shield ectopic tissue from immune clearance. ZEB1’s own roles in immune cell biology and in macrophage efferocytosis and mitochondrial dynamics add further dimensions to this immunological interplay.

A distinctive strength of the review is its engagement with modern genomics and the heterogeneity it has revealed. Single-cell transcriptomic analyses of endometriosis, published in Nature Genetics and the Journal of Pathology, have identified distinct hormonal, immunologic and inflammatory signatures among the cell populations constituting lesions, and spatial transcriptomics is beginning to map how intermediate fibroblast and myeloid cell distributions shape lesion architecture. ZEB1 expression, the authors note, is not uniform: it varies by lesion subtype, anatomical site and microenvironmental context, which helps explain why superficial peritoneal, ovarian endometrioma and deep infiltrating disease behave so differently and respond so unevenly to therapy. This heterogeneity argues strongly against a one-size-fits-all anti-ZEB1 strategy and supports the emerging precision-medicine framing of the oestrogen-ZEB1-TGF-β axis as the central therapeutic target.

The review is refreshingly candid about the translational paradox at the heart of any ZEB1-directed therapy. Far from being a purely pathological molecule, ZEB1 has indispensable physiological functions in the female reproductive tract. In vitro studies show that ZEB1 modulates endometrial receptivity through EMT in endometrial epithelial cells, and work in mice demonstrates that it promotes EMT of endometrial epithelium and plays a critical role in embryo implantation. ZEB1 is also detected in granulosa cells of women undergoing IVF, regulates wound angiogenesis and closure, participates in corneal homeostasis, and contributes to endometrial repair during menstruation through epithelial migration and mesenchymal–epithelial transition. Blanking ZEB1 systemically, therefore, risks impairing fertility, tissue regeneration and wound healing—the very outcomes clinicians are trying to protect. Any therapeutic strategy would need to be lesion-specific, temporally controlled and carefully titrated, perhaps by targeting upstream oestrogen-driven induction, the TGF-β/ALK5 arm, the non-coding RNA sponges, or post-translational stabilisation mechanisms such as ZEB1 acetylation, phosphorylation and ubiquitin-proteasome turnover via regulators like USP51 and SIAH1/2.

The authors also stress the need for better experimental models to establish causal rather than merely correlative relevance. shRNA- and siRNA-based knockdown of ZEB1 in endometriotic cells, three-dimensional patient-derived endometriosis models for drug evaluation, and multi-omics approaches that integrate transcriptomic, epigenomic and proteomic data—including recent ubiquitination-focused studies of endometriosis fibrosis—are all highlighted as tools that could convert the ZEB1 hypothesis into testable interventions. Biomarker development is another avenue: ZEB-family levels in plasma and peritoneal fluid, in combination with existing miRNA signatures, could one day support non-invasive diagnosis, a long-standing unmet need given that current detection still relies on laparoscopy.

Ultimately, the review’s central claim is that the oestrogen–ZEB1–TGF-β axis functions as a signalling hub through which the hormonal, inflammatory and epigenetic drivers of endometriosis converge and perpetuate one another. By identifying ZEB1 as the point of integration, the authors provide a mechanistic scaffold that could explain progesterone resistance, fibrotic progression and recurrence within a single framework, and they chart a cautious but concrete path toward mechanism-based, lesion-specific precision therapies. For a disease that has historically been managed with blunt hormonal and surgical instruments, the prospect of intervening at the level of a single, druggable transcriptional circuit represents one of the more compelling conceptual advances in endometriosis research in recent years.