Rupert Smit, MD (@rd_smitMD) header
Rupert Smit, MD (@rd_smitMD) profile picture

Founder at Appraiseye | Formerly @UoLondon & @BU_Tweets |🇨🇭🇿🇦 🇺🇸

Joined September 2021
Photo by Rupert Smit, MD (@rd_smitMD)Photo by Rupert Smit, MD (@rd_smitMD)Photo by Rupert Smit, MD (@rd_smitMD)Photo by Rupert Smit, MD (@rd_smitMD)Photo by Rupert Smit, MD (@rd_smitMD)Photo by Rupert Smit, MD (@rd_smitMD)Photo by Rupert Smit, MD (@rd_smitMD)Photo by Rupert Smit, MD (@rd_smitMD)Photo by Rupert Smit, MD (@rd_smitMD)Photo by Rupert Smit, MD (@rd_smitMD)
Proud to share Appraiseye’s seminal publication in the Journal of Neurosurgery 🚀 Our AI vision stack quantified what happens between cases; itemizing OR turnover into discrete subprocesses. Result: instrument burden is the main contributor to turnover duration ⏱️ Across 53 turnovers (cranial, spine, ENT): • Setup time explained most variability • Each additional tray added ~2.7 minutes • Tray count—not individual surgeon nor assigned OR— best predicted turnover Tray rationalization = faster turnover + lower costs researchgate.net/publication…
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Rupert Smit, MD retweeted
Three people with epilepsy resistant to drug treatment saw the number of seizures they had per month fall by more than 90%, after gene-laden viruses were infused directly into their brains go.nature.com/4z8SwhQ
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A major milestone for Chemogenetics. DREADD technology demonstrates therapeutic efficacy in humans. A new study published today in NEJM demonstrates preliminary safety and therapeutic benefit from DREADD-based chemogenetic treatment of refractory epilepsy, marking an extraordinary milestone for neuroscience and precision medicine. nejm.org/doi/full/10.1056/NE… The approach combines targeted AAV gene delivery at the epileptogenic locus with very low, subthreshold doses of clozapine to activate engineered DREADD receptors and modulate neuronal activity. Congratulations to Bryan Roth, whose pioneering discovery of DREADDs made this field possible, and to the investigators of the NEJM study for bringing this technology to patients. This achievement has a particularly meaningful connection to our work published in Science Magazine in 2017. science.org/doi/10.1126/scie… We showed that clozapine, rather than CNO itself, is the active mediator of DREADD activation in vivo and proposed that subthreshold doses of clozapine could be used to activate DREADDs in humans, anticipating a practical path toward clinical translation. At the time, many in the scientific community viewed these findings primarily as relevant to the design of preclinical DREADD experiments. We saw a much broader opportunity, translating Chemogenetics into human therapeutics. Nearly a decade later, that vision is now becoming a reality. Our 2017 study was supported by the research funding through the National Institutes of Health (NIH) and The National Institute on Drug Abuse (NIDA), a prime example of how fundamental basic research can ultimately enable transformative clinical applications. This is an exciting beginning, but larger, well-controlled studies are essential to establish the magnitude and durability of therapeutic benefit and long-term safety. Chemogenetics is moving beyond an experimental neuroscience tool toward a potentially transformative neuroscience platform. We are only beginning to realize its potential.
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amazing product launch today from @OpenEvidence for all the lifelong learners in medicine 📙
Introducing Learn, a free, personalized medical education platform from OpenEvidence, built to support trainees and clinicians across their entire careers. As AI changes how doctors work, it matters just as much that it strengthens how they learn. Clinicians have made OpenEvidence an everyday tool at the point of care. Now we apply that same technology and those same principles to how doctors learn medicine. Developed with leading medical institutions, certifiers, and educators, Learn brings together a suite of tools built on OpenEvidence so every trainee and clinician gets a tailored, evidence-based learning experience.
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Replying to @_jasonwei
Great post…thanks for sharing your thoughts. If I may opine on this as a radiologist with some technical understanding of LLMs/VLMs: I agree radiologists will not be automated away anytime soon. Your elastic demand point is mostly right (some modalities impart ionizing radiation so there is a good reason to not scan as frequently as you want), and I’d add a more fundamental one. The current transformer-based AI algorithms are extremely sample-inefficient compared to humans, especially when it comes to vision tasks (as opposed to text-based tasks). When I was a radiology resident, I read maybe 3000 CTs of the chest, abdomen and pelvis to reach expert/attending level. I can also make a rare-disease diagnosis after having seen 1 example study (or none; I can make a real-life diagnosis purely from reading and seeing an example case from a textbook). Currently, the best radiology VLM models, such as Nvidia’s NV-Reason-CT model, do not reliably call even some of the most common pathologies, despite having trained on >70,000 CTs that surely contain many examples of a common finding (macro-F1 of 0.614). I can think of several reasons for this: these models usually leverage weakly supervised learning such as CLIP, pairing radiology reports with the images, since wide-scale expert annotation is impractical for every study for every finding (Radiology’s Bitter Lesson, if you will; however, the signal that can scale is the noisy one). To scale, the model(s) will need to learn to associate image findings with words in the radiology reports. However, using radiology reports as ground truth can substantially limit learning. (1) As any radiologist will tell you, we don’t mention everything that we see. Otherwise, your radiology report would be like 30 pages long and not clinically useful. We mostly call the things that matter (for the most part). Sometimes, we don’t even call things that matter. Thus, some reports may mention “diverticulosis” when there is diverticulosis, while other reports don’t, even if there are findings of diverticulosis in the images. (2) Another limitation is that the actual real ground truth is never confirmed, which I suspect is a much bigger problem and harder to correct. When I was a radiology resident, I saved many cases in which my attendings and I made a certain call, and I was curious if those were correct. Right before I was about to graduate, I checked every case I had logged. Many calls were incorrect (and I trained at a major academic center in which subspecialized radiologists read their part of the body, so the attendings making those calls are above-average radiologists; real-world data is likely much worse). (1) and (2) make training very difficult when there is so much incorrectness, ambiguity and noise in the training data. The above observations are pretty self-evident when you look at other vision tasks, such as self-driving, for which there is (1) ample data with predominantly correct actions (labels), and (2) known ground truths (the task of driving is, for the most part, unambiguous. You see a red light, you stop. You want to make a left turn? You signal and yield to passing cars before turning. Those are universally agreed-upon “correct” actions). To use Tesla FSD as an example: even with the best compute, engineers and data, it took over a decade to reach limited, geofenced driverless service. And this is despite the fact that driving has a much shorter tail than radiology does. Further, self-driving usually has one correct action at a time. In radiology, that’s not true. There are so many different radiological appearances of one disease, as well as the same appearances of different diseases. And various diseases can involve the same anatomical location (for example, look up adrenal collision tumor). To “automate radiology” is also a huge simplification. The vast breadth of radiological studies is seldom mentioned. For a single modality of a body part, there are so many different variants. Say, for example, CT of the abdomen and pelvis: there are at least 10 different flavors of this. To name a few, there is the non-contrast CT, the portal venous phase CT (bread-and-butter workhorse), and then there are specialized versions such as the liver mass protocol, CT angiogram GI bleed protocol, pancreatic mass protocol CT, adrenal mass protocol CT, kidney mass protocol CT, and CT urogram, each of which contains 3-4 phases and is tailored to answer a specific question. All of this is just one modality for one section of the body. Now do ultrasound, X-rays, gamma studies, PET studies, and MRI. And then consider all the other body parts (brain, head and neck, chest, etc.). I’ve only touched upon the surface of all the nuances, but I think the current capability gap and your demand argument point the same way: radiologists will be busy for a long time.
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The “golden age of grift” may be coming to medicine. Prediction markets are now being introduced to clinical trials, creating opportunities for insider trading, conflicts of interest, and manipulation of trial outcomes. My new paper in @JCO_ASCO @ASCO: doi.org/10.1200/JCO-26-01303 pubmed.ncbi.nlm.nih.gov/4287… @profgalloway @edels0n
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BREAKING NEWS The 2026 #NobelPrize in Physiology or Medicine has been awarded to Karl Deisseroth, Peter Hegemann and Georg Nagel “for their discoveries concerning light-gated ion channels and optogenetics.”
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Exciting advance in neuroprosthetics: A Nature Medicine study reports that a brain–computer interface paired with neuromodulation helped one person with complete tetraplegia regain hand movement and some sensation. nature.com/articles/s41591-0…
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🌟 The future of AI in healthcare doesn’t have to be a choice between humans and machines. In a letter published in @Telegraph , SDSC Founder Dr. @ddonoho makes the case for a different vision of AI in healthcare: “AI should develop human expertise, not replace it.” 🩺 In surgery, that means turning what happens in the operating room into something others can learn from: giving surgeons better feedback, enabling them to learn from thousands of procedures beyond those they personally witness, and making specialist knowledge available far beyond the hospitals where it originates. Surgical expertise already exists around the world. The opportunity is to build the infrastructure, partnerships, and AI tools that allow more people to benefit from it. 👉 Read Dan’s letter in The Telegraph: telegraph.co.uk/opinion/2026… If your institution records neurosurgical or other minimally invasive procedures, your video could help answer research questions we haven't yet been able to ask at scale. Contribute surgical video and collaborate with us. 👉 surgicalvideo.io/research #SurgicalAI #GlobalHealthEquity #AIforGood
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NEW: Reed Jobs, a prominent biotech investor (and son of another Jobs you may have heard of), calls for a doubling of the NIH budget to $100 billion. Via @statnews statnews.com/2026/09/21/nih-…
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Super excited that #VirtualBiotech is published in @ScienceMagazine today! Tens of thousands of AI scientist agents work together across drug discovery + development, from target discovery to clinical trial design. Our blueprint for agentic R&D 🧵
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An extraordinary @Nature paper has just landed from the lab of @Sergiu_P_Pasca at @Stanford - led by Konstantin Kaganovsky. They have found a way to create "xenocortical mice" which have ~92% of their cortex occupied by a cortical organoid derived from human stem cells. This human-derived cortical graft integrates deeply with the host nervous system, supporting organised neural activity and behaviour. This study is a milestone in synthetic biology and chimera research. It has the potential to generate multiple medical breakthroughs by providing an enhanced biological model of human brain tissue that allows behavioural as well as neural and genetic assays. The Stanford team have been exceptionally thorough and proactive in addressing ethical concerns that comes from this frontier work. But their pioneering work nonetheless raises many open questions: are the xenocortical mice conscious? Do they have any human-like properties of consciousness or cognition? @NitaFarahany and I will be addressing some of these questions in a forthcoming commentary - where we'll also offer an ethically-informed roadmap to guide this important research as it progresses. In this context, "pacing the frontier" really does make sense 😉 Read the Stanford @nature paper here, and buckle up. It's wild. nature.com/articles/s41586-0…
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We built high-throughput materials labs in Menlo Park to create a loop between experiments and models. The labs generate fresh data, the models learn from it, and then help us decide what to try next. Using only 1,300 H200s, plus months of our experimental data, we mid-trained and RL’d an open-source model to surpass GPT-6 Astra on our analysis benchmark. We call it Neon. This is real footage from our lab. We’re focusing first on hard problems in materials science, including superconductors, magnets, and semiconductor materials. Read our blog posts below.
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We are on the cusp of a wave of new therapies for some of the worst diseases. But the world won’t benefit unless the US fixes its drug regulatory system. My new essay for @nytimes, on how slow clinical trials are now the biggest obstacle to curing cancer. nytimes.com/2026/09/04/opini… - I interviewed dozens of researchers, especially oncologists at leading U.S. centers. A striking consensus emerged: science is no longer the main bottleneck to new cancer drugs. It is our ability to test discoveries in patients through clinical trials. - The cost of starting a Phase 1 trial in America has roughly doubled over the past decade. As a result, companies increasingly take early trials abroad: Australia’s Phase 1 trial volume has nearly doubled in a decade, driven mainly by U.S. companies. - Unfortunately, the underlying incentives are badly asymmetric: Institutions can be blamed for harms caused by moving too fast, but almost no one is blamed when patients deteriorate during avoidable delays. One doctor called the emerging system “ritualized safety over actual risk assessment.” Or as, @DavidHongMD put it: "We often forget that the biggest risk is the cancer itself." - This problem is becoming more urgent because medicine itself is changing. Sequencing, biological engineering and A.I. make increasingly personalized therapies possible. But our regulatory system was mostly built for standardized drugs tested in large populations. - @sytse, the co-founder of GitLab, shows what personalized medicine can achieve: after relapsed osteosarcoma and being told there were no options left, he pursued a highly individualized approach and has now been cancer-free for a year. But doing so required extraordinary resources and regulatory expertise. - Pierce Ogden’s father was less lucky. After molecular analysis identified a drug that might target his glioblastoma, the manufacturer agreed to provide it. But administrative barriers delayed access until it was too late. “My dad was ready to try anything,” Pierce told me. “But the system is paternalistic.” - The A.I. revolution is making this bottleneck more important, not less. A.I. relies on relevant data. Information from early-stage trials could compound with A.I. tools to achieve truly revolutionary medicines. Without the data, this is far less likely to happen. - Another important shift is that innovation increasingly comes from academic labs and small biotech companies rather than Big Pharma. These small companies find it far harder to unable to absorb delays and regulatory barriers. - Apart from cancer, China is the biggest winner from America's outdated medical regulations. China has a much faster trial system, with testing often starting a full year earlier. This allows Chinese pharmaceutical companies to experiment and improve medicines while American companies play with mice. Today, half of all drugs licensed by major pharmaceutical companies originate there, up from less than 5 percent only a decade ago. - But we don't need to copy China. The best model is Australia: lots of on-site scientific and ethics reviews, and requirements that are proportionate to small, early-stage trials. Phase 1 studies there begin roughly 6–12 months faster, without any notable increases in adverse safety events. - Operation TrialBlazer, a 2026 HHS initiative is a good start in this direction, but we need legislative action by Congress to truly make Phase I trials faster and more efficient! I want to thank everyone who helped me with this article: everyone I interviewed and the amazing editors at the Times. This is the result of a months long journey of extensive interviews and research. Special thanks go to those who came on the record. One of the features of the system is an atmosphere of fear, where practitioners are afraid to publicly come out and explain these issues. So anyone who does is a hero in my book!
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From precise causal circuit studies → human network mapping → personalized therapy. Our new @brainstimj study from the Human Neural Circuitry Program creates a rapid, clinically feasible 3-day stereo-EEG mapping approach to personalize multinodal stimulation for refractory facial pain. Excited to see the growing clinical impact of optogenetics, beyond revolutionizing basic neuroscience, with foundational studies of neuropathic pain—including work from Zamponi, Deisseroth & Zhang (Nature Neuroscience, 2019)--informing human circuit sampling. Thanks Laura Sanders @ScienceNews for the interest in our work —and what this approach could mean for the future of precision neuromodulation. 🔗 Paper: brainstimjrnl.com/article/S1… sciencenews.org/article/brai…
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Regenerative Neural Stem Cell Therapy Improves Multidomain Neurological Deficits after Traumatic Brain Injury in Nonhuman Primates biorxiv.org/content/10.64898…
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Today, we're kicking off the first phase of the research preview for Model Hardware Standard (MHS): a new standard for AI agents to safely operate physical equipment in scientific research and advanced manufacturing. Read more: anthropic.com/news/model-har…
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medical geneticists are where AI researchers were 20 years ago: tucked away in institutional basements, but soon to emerge front and center
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Nature research paper: In vivo feasibility study of humanoid robots in surgery go.nature.com/4aHF0Z6
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From routine clinical care to groundbreaking discovery. A new @NatureMedicine publication from @ToddCHollon and collaborators highlights how decades of clinical neuroimaging data can help build the next generation of AI for medicine. Congratulations to the research team and to our faculty whose contributions helped make this groundbreaking work possible. @umichneuro @UMichMedSchool @umichmedicine Read more: nature.com/articles/s41591-0…
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There’s a cafe in Shenzen’s biotech hub that gives you free coffee for a month if you publish in Nature or Science.
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