Alan Karthikesalingam

Alan Karthikesalingam

Alan is a Principal Scientist and Director at Google DeepMind working on biomedical AI. He cofounded and leads AI co-clinician and AI co-scientist; and previously founded and led precursors in AMIE, Med-PaLM, Med-PaLM-2 and Med-PaLM-Multimodal. His research in over 10 full Nature/Nature-Medicine publication spans breakthroughs for conversational and diagnostic AI systems in multiple domains. These include the first example of an AI system passing medical license-style examinations, competently undertaking medical consultations, and solving multimodal diagnostic challenges spanning cardiology, radiology, oncology, ophthalmology, dermatology and electronic health records. He is an honorary Lecturer in Vascular Surgery at Imperial College in London. He completed his MA in Neuroscience and Medical Degree (MBBChir) at the University of Cambridge before specialist training in surgery in the London Deanery, where he completed his Membership of the Royal College of Surgeons (MRCS), PhD in Vascular Surgery and appointment as NIHR Clinical Lecturer. Prior to joining Google DeepMind Alan had published over 150 peer-reviewed articles including first-author studies in the New England Journal of Medicine and The Lancet.

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CoDaS: AI Co-Data-Scientist for Biomarker Discovery via Wearable Sensors
Juro Gottweis
CJ Park
Salman Rahman
Ahmed Metwally
Hong Yu
Ivor Rendulic
Yuzhe Yang
Petar Sirkovic
Daniel McDuff
Shwetak Patel
Nicolas Stroppa
Yubin Kim
Mark Malhotra
Orson Xu
Sam Schmidgall
Tim Althoff
Elahe Vedadi
Cynthia Breazeal
Hae Won Park
(2026)
Preview abstract While large language models (LLMs) have shown promise in diagnostic dialogue, their capabilities for effective management reasoning - including disease progression, therapeutic response, and safe medication prescription - remain under-explored. We advance the previously demonstrated diagnostic capabilities of the Articulate Medical Intelligence Explorer (AMIE) through a new LLM-based agentic system optimised for clinical management and dialogue, incorporating reasoning over the evolution of disease and multiple patient visit encounters, response to therapy, and professional competence in medication prescription. To ground its reasoning in authoritative clinical knowledge, AMIE leverages Gemini's long-context capabilities, combining in-context retrieval with structured reasoning to align its output with relevant and up-to-date clinical practice guidelines and drug formularies. In a randomized, blinded virtual Objective Structured Clinical Examination (OSCE) study, AMIE was compared to 21 primary care physicians (PCPs) across 100 multi-visit case scenarios designed to reflect UK NICE Guidance and BMJ Best Practice guidelines. AMIE was non-inferior to PCPs in management reasoning as assessed by specialist physicians and scored better in both preciseness of treatments and investigations, and in its alignment with and grounding of management plans in clinical guidelines. To benchmark medication reasoning, we developed RxQA, a multiple-choice question benchmark derived from two national drug formularies (US, UK) and validated by board-certified pharmacists. While AMIE and PCPs both benefited from the ability to access external drug information, AMIE outperformed PCPs on higher difficulty questions. While further research would be needed before real-world translation, AMIE's strong performance across evaluations marks a significant step towards conversational AI as a tool in disease management. View details
Towards Physician-Level Medical Question Answering with Large Language Models
Karan Singhal
Juro Gottweis
Le Hou
Kevin Clark
Heather Cole-Lewis
Amy Wang
Sami Lachgar
Philip Mansfield
Sushant Prakash
Bradley Green
Ewa Dominowska
Nenad Tomašev
Renee Wong
Sara Mahdavi
Joelle Barral
Nature Medicine (2025) (to appear)
Preview abstract Recent artificial intelligence (AI) systems have reached milestones in "grand challenges" ranging from Go to protein-folding. The capability to retrieve medical knowledge, reason over it, and answer medical questions comparably to physicians has long been viewed as one such grand challenge. Large language models (LLMs) have catalyzed significant progress in medical question answering; Med-PaLM was the first model to exceed a "passing" score in US Medical Licensing Examination (USMLE) style questions with a score of 67.2% on the MedQA dataset. However, this and other prior work suggested significant room for improvement, especially when models' answers were compared to clinicians' answers. Here we present Med-PaLM 2, which bridges these gaps by leveraging a combination of base LLM improvements (PaLM 2), medical domain finetuning, and prompting strategies including a novel ensemble refinement approach. Med-PaLM 2 scored up to 86.5% on the MedQA dataset, improving upon Med-PaLM by over 19% and setting a new state-of-the-art. We also observed performance approaching or exceeding state-of-the-art across MedMCQA, PubMedQA, and MMLU clinical topics datasets. We performed detailed human evaluations on long-form questions along multiple axes relevant to clinical applications. In pairwise comparative ranking of 1066 consumer medical questions, physicians preferred Med-PaLM 2 answers to those produced by physicians on eight of nine axes pertaining to clinical utility (p < 0.001). We also observed significant improvements compared to Med-PaLM on every evaluation axis (p < 0.001) on newly introduced datasets of 240 long-form "adversarial" questions to probe LLM limitations. While further studies are necessary to validate the efficacy of these models in real-world settings, these results highlight rapid progress towards physician-level performance in medical question answering. View details
Preview abstract Generative Artificial Intelligence (AI), particularly Large Language Models (LLMs), have demonstrated significant potential in clinical reasoning skills such as history-taking and differential diagnosis generation—critical aspects of medical education. This work explores how LLMs can augment medical curricula through interactive learning. We conducted a participatory design process with medical students, residents and medical education experts to co-create an AI-powered tutor prototype for clinical reasoning. As part of the co-design process, we conducted a qualitative user study, investigating learning needs and practices via interviews, and conducting concept evaluations through interactions with the prototype. Findings highlight the challenges learners face in transitioning from theoretical knowledge to practical application, and how an AI tutor can provide personalized practice and feedback. We conclude with design considerations, emphasizing the importance of context-specific knowledge and emulating positive preceptor traits, to guide the development of AI tools for medical education. View details
Towards Conversational Diagnostic AI
Khaled Saab
Jan Freyberg
Ryutaro Tanno
Amy Wang
Brenna Li
Nenad Tomašev
Karan Singhal
Yong Cheng
Le Hou
Albert Webson
Kavita Kulkarni
Sara Mahdavi
Juro Gottweis
Joelle Barral
Kat Chou
Nature (2025) (to appear)
Preview abstract At the heart of medicine lies the physician-patient dialogue, where skillful history-taking paves the way for accurate diagnosis, effective management, and enduring trust. Artificial Intelligence (AI) systems capable of diagnostic dialogue could increase accessibility, consistency, and quality of care. However, approximating clinicians' expertise is an outstanding grand challenge. Here, we introduce AMIE (Articulate Medical Intelligence Explorer), a Large Language Model (LLM) based AI system optimized for diagnostic dialogue. AMIE uses a novel self-play based simulated environment with automated feedback mechanisms for scaling learning across diverse disease conditions, specialties, and contexts. We designed a framework for evaluating clinically-meaningful axes of performance including history-taking, diagnostic accuracy, management reasoning, communication skills, and empathy. We compared AMIE's performance to that of primary care physicians (PCPs) in a randomized, double-blind crossover study of text-based consultations with validated patient actors in the style of an Objective Structured Clinical Examination (OSCE). The study included 149 case scenarios from clinical providers in Canada, the UK, and India, 20 PCPs for comparison with AMIE, and evaluations by specialist physicians and patient actors. AMIE demonstrated greater diagnostic accuracy and superior performance on 28 of 32 axes according to specialist physicians and 24 of 26 axes according to patient actors. Our research has several limitations and should be interpreted with appropriate caution. Clinicians were limited to unfamiliar synchronous text-chat which permits large-scale LLM-patient interactions but is not representative of usual clinical practice. While further research is required before AMIE could be translated to real-world settings, the results represent a milestone towards conversational diagnostic AI. View details
Preview abstract Note this is a re-submission of a previously approved ITP. The previous approval was conditional for a journal pre-sub enquiry only and we are submitting a new ITP for the preprint of the paper. AI models have been proposed for hypothesis generation, but testing their ability to drive high-impact research is challenging, since an AI-generated hypothesis can take decades to validate. Here, we challenge the ability of a recently developed LLM-based platform to generate high-level hypotheses by posing a question that took years to resolve experimentally but remained unpublished: How could capsid-forming phage-inducible chromosomal islands (cf-PICIs) spread across bacterial species? Remarkably, the AI’s top- ranked hypothesis matched our experimentally confirmed mechanism: cf-PICIs hijack diverse phage tails to expand their host range. We critically assess the AI’s five highest- ranked hypotheses, showing that some opened new research avenues in our laboratories. We benchmark its performance against other LLMs and outline best practices for integrating AI into scientific discovery. Our findings suggest that AI can act not just as a computational tool, but as a creative engine, accelerating discovery and reshaping how we generate and test scientific hypotheses. View details
Safety principles for medical summarization using generative AI
Dillon Obika
Christopher Kelly
Nicola Ding
Chris Farrance
Praney Mittal
Donny Cheung
Heather Cole-Lewis
Madeleine Elish
Nature Medicine (2024)
Preview abstract The introduction of Generative AI, particularly large language models presents exciting opportunities for healthcare. However their novel capabilities also have the potential to introduce novel risks and hazards. This paper explores the unique safety challenges associated with LLMs in healthcare, using medical text summarization as a motivating example. Using MedLM as a case example, we propose leveraging existing standards and guidance while developing novel approaches tailored to the specific characteristics of LLMs. View details
Preview abstract Large language models (LLMs) hold promise to serve complex health information needs but also have the potential to introduce harm and exacerbate health disparities. Reliably evaluating equity-related model failures is a critical step toward developing systems that promote health equity. We present resources and methodologies for surfacing biases with potential to precipitate equity-related harms in long-form, LLM-generated answers to medical questions and conduct a large-scale empirical case study with the Med-PaLM 2 LLM. Our contributions include a multifactorial framework for human assessment of LLM-generated answers for biases and EquityMedQA, a collection of seven datasets enriched for adversarial queries. Both our human assessment framework and our dataset design process are grounded in an iterative participatory approach and review of Med-PaLM 2 answers. Through our empirical study, we find that our approach surfaces biases that may be missed by narrower evaluation approaches. Our experience underscores the importance of using diverse assessment methodologies and involving raters of varying backgrounds and expertise. While our approach is not sufficient to holistically assess whether the deployment of an artificial intelligence (AI) system promotes equitable health outcomes, we hope that it can be leveraged and built upon toward a shared goal of LLMs that promote accessible and equitable healthcare. View details
Understanding metric-related pitfalls in image analysis validation
Annika Reinke
Lena Maier-Hein
Paul Jager
Shravya Shetty
Understanding Metrics Workgroup
Nature Methods (2024)
Preview abstract Validation metrics are key for the reliable tracking of scientific progress and for bridging the current chasm between artificial intelligence (AI) research and its translation into practice. However, increasing evidence shows that particularly in image analysis, metrics are often chosen inadequately in relation to the underlying research problem. This could be attributed to a lack of accessibility of metric-related knowledge: While taking into account the individual strengths, weaknesses, and limitations of validation metrics is a critical prerequisite to making educated choices, the relevant knowledge is currently scattered and poorly accessible to individual researchers. Based on a multi-stage Delphi process conducted by a multidisciplinary expert consortium as well as extensive community feedback, the present work provides the first reliable and comprehensive common point of access to information on pitfalls related to validation metrics in image analysis. Focusing on biomedical image analysis but with the potential of transfer to other fields, the addressed pitfalls generalize across application domains and are categorized according to a newly created, domain-agnostic taxonomy. To facilitate comprehension, illustrations and specific examples accompany each pitfall. As a structured body of information accessible to researchers of all levels of expertise, this work enhances global comprehension of a key topic in image analysis validation. View details
Generative models improve fairness of medical classifiers under distribution shifts
Ira Ktena
Olivia Wiles
Isabela Albuquerque
Sylvestre-Alvise Rebuffi
Ryutaro Tanno
Danielle Belgrave
Taylan Cemgil
Nature Medicine (2024)
Preview abstract Domain generalization is a ubiquitous challenge for machine learning in healthcare. Model performance in real-world conditions might be lower than expected because of discrepancies between the data encountered during deployment and development. Underrepresentation of some groups or conditions during model development is a common cause of this phenomenon. This challenge is often not readily addressed by targeted data acquisition and ‘labeling’ by expert clinicians, which can be prohibitively expensive or practically impossible because of the rarity of conditions or the available clinical expertise. We hypothesize that advances in generative artificial intelligence can help mitigate this unmet need in a steerable fashion, enriching our training dataset with synthetic examples that address shortfalls of underrepresented conditions or subgroups. We show that diffusion models can automatically learn realistic augmentations from data in a label-efficient manner. We demonstrate that learned augmentations make models more robust and statistically fair in-distribution and out of distribution. To evaluate the generality of our approach, we studied three distinct medical imaging contexts of varying difficulty: (1) histopathology, (2) chest X-ray and (3) dermatology images. Complementing real samples with synthetic ones improved the robustness of models in all three medical tasks and increased fairness by improving the accuracy of clinical diagnosis within underrepresented groups, especially out of distribution. View details
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