Research Translation Podcast

About Research Translation Podcast

Translating Medical and Health Research For All researchtranslation.substack.com (https://researchtranslation.substack.com?utm_medium=podcast)

Publisher

David Newman

Category

health & fitness · science

Language

en

Explicit

No

First episode

7 May 2024

Latest episode

28 Oct 2026

Latest episodes

107 episodes in the feed.

1. 

   28 Oct 2026

   My Run-In With Elizabeth Holmes

   I met Elizabeth Holmes once, for about four seconds. It was 2013, I believe, at a Wired Health conference. Wired had profiled me and TheNNT (https://www.wired.com/2014/10/number-needed-to-treat/), a website colleagues and I built to make medical evidence transparent and free, and they asked me to give a talk about evidence and data (you can see a 3-minute excerpt here (https://www.youtube.com/watch?v=Cb_HZUjgglA&t=188s)). Holmes was on the same bill and spoke earlier in the day. We were introduced in the green room. That was pretty much the whole conversation. What I remember is not so much her, as the men around her. Earpieces, dark suits, scanning the room for threats. A security detail like the ones you might see around a cabinet secretary. I remember sitting with my Coke Zero and musing to myself what, exactly, the CEO of a blood-testing company needed protection from. In hindsight, the answer was obvious. She needed protection from scientific reality. After my talk I took questions from the floor. The first few were polite, perhaps feigning interest in the much dryer topic of translating research data. Then a few people in the audience, investors and VC types by the look of them, asked me what I thought of her company. To be honest I knew nothing about Theranos before that day. But two things struck me as self-evident. The first was that I read the medical literature obsessively, and there was nothing in it about rapid serum testing with a drop of blood. No validation studies. No peer-reviewed data. A company claiming to have reinvented laboratory medicine had, to my eye, published nothing about it. The second thing I knew was my own job. By then I had spent 15 years in emergency departments and about 25 in health care, counting paramedicine and the military. Every shift, we drew blood on sick people and then waited for the tubes go to a lab and, 45 minutes later, if we were lucky, we got numbers to help us tell whether someone was bleeding, infected, poisoned, or worse. So I told them what seemed obvious. If she really had a device that gave instant, reliable answers to hundreds of tests from a finger-prick, it seemed to me it would already be in my ER, and every other one on the planet. She wouldn’t need to raise money, and have a $9 billion valuation. She would be selling $200 billion worth of product, today. Real breakthroughs don’t hide. They get used. Then I asked THEM something, and I was not playing dumb. Am I missing something? Is her product just a blood test? Yes, they said. It’s a blood test. Well then, I said, I don’t get it. Because you can’t save a life with a blood test. Holmes talked as if information were treatment. Her signature story was about her uncle, who died of cancer, and she implied that if only her machine was at his side, testing him again and again, he never would have had cancer, or died of it. That is, to be blunt, just dumb. Anyone who’s done real work in medical evidence learns quickly that there is no perfect test. Every test misses some disease that’s present, and flags some that isn’t. Our fanciest and newest high tech blood test for cancer, the Galleri MCED (https://researchtranslation.substack.com/p/the-early-detection-cancer-test-that), missed more than half of growing cancers, and more than half of those it flagged were false alarms. There was no cancer. This kind of performance is typical for virtually all blood tests. Had Holmes, I asked, invented some new version of cancer testing that was 100% accurate? That she was hiding somewhere, instead of releasing it for all the world to use? Moreover, I said, even when a test finds something real, we usually don’t know what it means. Every tumor is staggeringly complex. So is every human body. When the two meet, we have no idea how the two will interact. The immune system might quietly destroy the tumor, or it might sit harmlessly for decades, or it might take over the body, fast. If we could predict cancer-human interactions we would treat the dangerous tumors and leave the rest alone, and every cancer screening test would be a smashing success. But we can’t predict which, so we treat nearly everything we find, doing countless surgeries, scopes, and scans, and most of the people we ‘save’ were never in danger. We are standing on a tiny island of knowledge in a vast sea of information. More testing simply pours more water into the sea. It doesn’t make the island any bigger. Holmes was selling water. Even if her machine worked flawlessly, the promise underneath it would have been false. It would be nice if we could file Theranos under fraud and move on. Holmes lied, she was convicted, she went to prison. Case closed. But the investors I met that day were sharp. One introduced herself to me as a “recovered cardiologist,” which I loved. She was funny, self-aware, and had spent years seeing up close what medicine can and can’t do. If anyone should have been immune to the pitch, it was her. Yet there she was with the rest of them, putting real money into the idea that the next gadget (a blood test!) would change everything. That’s the part we should all sit with. This isn’t a story about gullible people. It’s about a way of thinking that we all share, smart people included, and it’s very hard to see in ourselves. Call it gizmo idolatry (https://jamanetwork.com/journals/jama/article-abstract/181743). The quiet faith that medicine is more powerful than it is. Or that a certain surgeon has magic hands. Or a special test will catch the thing that would have killed you. Or a treatment is so good it can’t possibly hurt you. Or more blood testing means more living. And if we’re being honest with ourselves, it’s a reasonable mistake. You carry a phone that can call China at three in the morning, stream a film, and find your way home. It seems only natural to assume that the giant hospital systems, with their billions of dollars and research towers, are at least that impressive. Surely they can do more than the phone in my pocket. But they can’t. Not in the way we imagine. Trials of annual checkups (https://www.cochrane.org/about-us/news/featured-review-are-general-health-checks-beneficial) and screening programs find more diagnoses and more procedures, not longer lives. Prostate screening (https://www.uspreventiveservicestaskforce.org/uspstf/document/evidence-summary/prostate-cancer-screening) brings more biopsies, more surgery and more frightened men, but no clear gain in survival. The new multi-cancer blood tests are sold using the same emotional grammar Holmes used: one draw, dozens of cancers, catch it early. Yet randomized trials now show (https://www.nejm.org/doi/full/10.1056/NEJMoa2505723) it didn’t even catch cancer early, much less help anyone live longer. Holmes didn’t invent this faith. She just discovered it in a dorm at Stanford, and sold it back to us. The fraud was hers, but the magical thinking is ours. And it’s still for sale. I didn’t sniff out Theranos because I’m clever. I sniffed it out because I’ve spent a career watching tests not save people, and because I’ve learned to ask one boring question about any shiny new thing in medicine: Can you show me the people who lived longer because of it? Holmes never had that answer. Neither do most of the tests being sold to you right now. The security detail in that green room was protecting her from that question. But your doctor doesn’t have a security detail. So ask away. Get full access to Research Translation at researchtranslation.substack.com/subscribe (https://researchtranslation.substack.com/subscribe?utm_medium=podcast&utm_campaign=CTA_4)

2. 

   21 Oct 2026

   The Babies Who Died of Early Detection

   What follows is a summary of the transcript, written by Claude. Let me know what you think, please. RT is fully reader-supported. Please become a paid subscriber—and spread the word, yo. My sons, 11 and 13, inform me that when I say something like “cancer screening can kill you,” the phrase I’m looking for is “no cap.” I’m grateful, because half of what I say about cancer screening sounds unhinged next to what we’ve all been taught. So: no cap. Facts. Let me start with a story I first told in 2007, in a book called Hippocrates’ Shadow (https://www.simonandschuster.com/books/Hippocrates-Shadow/David-H-Newman/9781416551546). Nearly twenty years later, we still haven’t absorbed it. The urine test that found too much In 2002, two studies from Quebec (https://www.nejm.org/doi/abs/10.1056/NEJMoa012387) and Germany (https://www.nejm.org/doi/full/10.1056/NEJMoa012277) reported what happened when public-health officials screened infants’ urine for neuroblastoma, one of the leading causes of cancer death in young children. Japan ran a similar program. The idea was flawless: catch the tumours early, while small, and fewer babies should die. Screening worked brilliantly at finding cancer. Children in the screened groups were diagnosed about three times as often as children in the unscreened comparison groups, even after years of follow-up. These weren’t false alarms. A positive urine test led to imaging, the imaging led to a biopsy, and the biopsy confirmed neuroblastoma under the microscope. Neuroblastoma deaths didn’t move. Roughly two out of three screen-detected tumors would have vanished or never caused a symptom—but they were all treated, aggressively. In the German program, the only three screened children who died were killed by the treatment: two by surgical complications, one by chemotherapy. Neuroblastoma screening was shut down worldwide. Leg one: You’re already running a screening program How do you find three times as many cancers that don’t matter? Your body was already on the case. Immunosurveillance is the continuous process by which your immune system finds abnormal cells and destroys or contains them. We’ve seen the evidence from the other direction for decades: people with AIDS, and transplant patients on immune-suppressing drugs, get more cancers. Take the guards off and more cancers get through. We can’t watch this happen at the cellular level, so we don’t know how often it succeeds. It seems to work better for some tumors than others. Screen for breast or prostate cancer and you don’t just find cancers earlier. You find more of them, over a lifetime. That makes no sense if every cancer is headed for the morgue, and perfect sense if your body was quietly handling a lot of them. The innate system almost certainly outperforms any screening technology we’ve built. Our technology’s main contribution is finding cancers the immune system already had under control, then treating them as if it didn’t. That breaks the escalator model of cancer most of us carry around: stage 1, 2, 3, 4, then dead. Every screening program is built on that escalator. Leg two: The barnyard Gil Welch, and Vinay Prasad after him, often talk about sorting cancers into three animals. Turtles are so slow that you can catch them whenever you like, or never. Birds fly out of the barn before any test can catch them, often showing up between screens. Rabbits sit in the middle: lethal if you find them as a lump under a clinician’s fingertip, curable if you find them as a shadow on a mammogram. Screening exists for rabbits. (Nobody has yet demonstrated that they exist, but perhaps they do). Screening also catches turtles and birds by the bushel. Leg three: Counting the bodies properly Screening trials mostly measure cancer-specific mortality, meaning deaths from breast cancer or from prostate cancer. Go back to the German babies. Count only “deaths from neuroblastoma” and leave out the children killed by surgery and chemo, and screening looks like a triumph. That’s why I care about all-cause mortality. More than 700,000 men have been randomized in PSA trials and roughly 600,000 women in mammography trials. Neither group shows a reduction in overall deaths. Some trials show fewer cancer-specific deaths, and some don’t even show that. That leaves two possibilities. Either the harms of overdiagnosis and overtreatment cancel out the lives saved, or the benefit is real but too small to detect even in trials of hundreds of thousands of people. The debate among experts is not about whether all-cause mortality dropped. It didn’t. The debate is whether we should trust cancer-specific mortality as a stand-in. We tried that with neuroblastoma. It was wrong, so I don’t subscribe to that school of thinking. No free lunch Take the advocates’ best case. Over 10 years of mammography, about 1 woman in 1,500 avoids a breast cancer death. Of those same 1,500, about 750 get a false positive and the anxiety and workup that follow, and about 50-75 have a surgical procedure on a breast that turns out to be normal. For PSA, the USPSTF’s numbers (with a little back-calculation from me) say that for every 1,000 men screened for a decade, 1 fewer dies of prostate cancer. Meanwhile 125 more have biopsies, 35 more are diagnosed with cancer, 27 more have their prostate removed or irradiated, 6 more become impotent and 4 more become incontinent. If you see those numbers and say, “I just don’t want to die of this cancer, sign me up,” that’s a rational choice. Make it. But that isn’t the conversation people are having. This year my new primary care team at the VA, a health system I genuinely love, was about to send a PSA test without mentioning it. They pulled it the moment I asked. Still, the default was to test everyone and discuss it with no one. Consider the source Who tells you to get screened? Radiology societies recommend mammography, and urology societies recommend PSA testing. I’m not accusing anyone of lying. But Upton Sinclair observed that it’s hard to get someone to understand something when their paycheck depends on not understanding it. Professional recommendations and evidence are different things. So ask for the numbers. The USPSTF’s evidence reviews are free and open. Ask your doctor how many people like you avoid death from this cancer, how many avoid death from anything, and how many get false alarms, biopsies and treatments they didn’t need. Then bring your own values to the decision. Cancer screening isn’t the lollipop at the end of the visit. Ask the babies. If this made you smarter, restack it. Newcomers, welcome; old guard, thank you. And if you want Research Translation to keep growing, become a paid subscriber. Get full access to Research Translation at researchtranslation.substack.com/subscribe (https://researchtranslation.substack.com/subscribe?utm_medium=podcast&utm_campaign=CTA_4)

3. 

   14 Oct 2026

   The Early Detection Cancer Test That Doesn’t Detect Early

   In college our physics teacher, Professor McGinnis, held an annual competition. Using a container made only of glue and toothpicks, we had to keep an egg from cracking when dropped out of the classroom’s first-story window. My team built a geometric lattice, buttressed with layers of internal protection. It was beautiful. For our (mandatory) test run, we dropped it empty, to be sure the container would survive and the egg compartment would hold. The container fell apart, and the compartment was gone. So we redesigned. Again the empty drop failed. But the lattice was so pretty. Perhaps the weight of a settled egg would strengthen the wood, we hoped. And with no time for a loaded test, we prepared for Egg Drop Friday. Suzanne, our dropper, had magic hands. With a quick lift and a soft release, our soccer-ball-like structure seemed to fall slower than gravity should allow. All morning, cheers had erupted at each impact. But when our dazzler struck the ground, the crowd fell silent. Toothpicks everywhere. The egg was not cracked, it was obliterated. No piece of shell was larger than a coin. Professor McGinnis wondered aloud whether our structure had somehow funneled the energy straight into the egg. Then, shaking his head, he asked the question we all knew was coming. “What happened when you did the empty drop?” Last week the New England Journal of Medicine published NHS-Galleri (https://www.nejm.org/doi/full/10.1056/NEJMoa2505723), a massive trial that randomized more than 140,000 people in England to have, or not have, their blood run through a multi-cancer early detection (MCED) test once a year for three years. The trial was funded by the test’s manufacturer, Grail, and Grail employees are among the authors. Let’s start with what matters: The point of cancer screening is to keep people from dying. This paper doesn’t even report how many people died in each group, from cancer or from anything else. This is despite the fact that the trial enrolled 140,000 people, easily enough to have a count of cancer and overall mortality, Instead, they offer us a test run: did the early detection test detect cancer earlier? It is the empty egg drop. It failed. The primary outcome was whether annual testing reduced the number of people diagnosed with late-stage (stage III or IV) cancer. It didn’t, and it wasn’t a near miss. The screened people were found to have 706 late-stage cancer diagnoses and the unscreened people were diagnosed with 688. In other words there were MORE, LATER STAGE, cancers in the tested group. Grail’s press release (https://grail.com/press-releases/landmark-nhs-galleri-trial-demonstrates-a-substantial-reduction-in-stage-iv-cancer-diagnoses-increased-stage-i-and-ii-detection-of-deadly-cancers-and-four-fold-higher-cancer-detection-rate/), however, leads with something different. They tout “20% drop in stage IV cancers”! This was a secondary endpoint, and the result’s confidence interval brushes up against no effect at all. Moreover this reduction, they confess was “offset by a higher rate of stage III cancer diagnosis.” The test didn’t lift anyone out of late-stage disease. Why? The companion paper (https://www.nature.com/articles/s41591-026-04652-8#Sec20) in Nature Medicine shows us. In years two and three, which is what a real annual screening program looks like, the test missed about 73% of cancers, and roughly half of the 12 deadly types it was designed to catch. Worse yet, about half its positive results were false alarms: 864 healthy, cancer-free people were told they might have cancer. The test’s specificity, around 99.5%, sounds superb. But it isn’t. When you screen millions of healthy people for rare diseases, even 99.5% means half of all positive results are wrong. Scale it to 100 million Americans and roughly 450,000 people a year would be told they might have cancer when they don’t, each launched into scans, scopes, and biopsies. And Grail tuned the test for that specificity. The price was sensitivity, which is why it missed MOST cancers. This isn’t a bug to fix in version 2.0. Small, early tumors shed very little DNA into the blood. Crank up the sensitivity to find them and you drown in false positives and overdiagnosis, the treatment of ‘cancers’ that would never have hurt anyone. Cancer is not one disease marching in a straight line from small and curable to big and deadly. Some kill no matter how early you find them. Some never would have mattered. The mythical sweet spot, where finding it early changes everything, has never been proven to exist. And if it does, we know this: It’s way smaller than the brochures suggest. But fortunately for the test manufacturers, and unfortunately for us, early detection is more than a strategy. It’s an ideology, and for many it’s even a faith. And faith can ‘succeed’ even when the empty drop fails. Which brings us to September 23, exactly one day after the NEJM paper went online. An FDA advisory committee met to consider Grail’s application and voted to recommend approving (https://www.prnewswire.com/news-releases/fda-advisory-committee-votes-in-favor-of-approval-of-grails-galleri-multi-cancer-early-detection-test-302888303.html) the test. Someone on that panel should have asked Professor McGinnis’s question: What happened when you did the empty drop? Get full access to Research Translation at researchtranslation.substack.com/subscribe (https://researchtranslation.substack.com/subscribe?utm_medium=podcast&utm_campaign=CTA_4)

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