Shekoofeh Azizi

Artificial intelligence has high potential for impact in healthcare applications, but its training and deployment are challenging due to diverse data, a complex spectrum of possible tasks and important privacy needs. High-performing foundation models that enable data-efficient fine-tuning for diverse downstream tasks can meaningfully accelerate development in this domain. We introduce MedGemma, a collection of medical vision-language foundation models based on Gemma 3. MedGemma demonstrates advanced medical understanding and reasoning across images and text and multiple medical imaging domains, exceeding the performance of similarly sized generative models while maintaining the general capabilities of the Gemma base models. For out-of-distribution tasks, MedGemma achieves improvements of 2.6–10% in medical image question answering, 15.5–18.1% in chest X-ray finding classification and 10.8% in agentic evaluations compared with the base models. Our results show that fine-tuning MedGemma can be more effective than fine-tuning the base Gemma 3 model for medical tasks, particularly in the setting of limited training data. We additionally introduce MedSigLIP, a medically tuned vision encoder derived from SigLIP. MedSigLIP powers the visual understanding capabilities of MedGemma and, as an encoder, achieves performance comparable to or better than that of many specialized medical image encoders. Taken together, the MedGemma collection provides a strong foundation of medical image and text capabilities, with the potential to accelerate medical research and the development of downstream applications.

A bstract: Single-cell RNA sequencing has transformed our understanding of cellular diversity, yet current single-cell foundation models (scFMs) remain limited in their scalability, flexibility across diverse tasks, and ability to natively integrate textual information. In this work, we build upon the Cell2Sentence (C2S) framework, which represents scRNA-seq profiles as textual “cell sentences,” to train Large Language Models (LLMs) on a corpus comprising over one billion tokens of transcriptomic data, biological text, and metadata. Scaling the model to 27 billion parameters yields consistent improvements in predictive and generative capabilities and supports advanced downstream tasks that require synthesis of information across multi-cellular contexts. Targeted fine-tuning with modern reinforcement learning techniques produces strong performance in perturbation response prediction, natural language interpretation, and complex biological reasoning. This predictive strength enabled a dual-context virtual screen that nominated the kinase inhibitor silmitasertib (CX-4945) as a candidate for context-selective upregulation of antigen presentation. Experimental assessment in human cell models unseen during training supported this prediction, demonstrating that C2S-Scale can effectively guide the discovery of context-conditioned biology. C2S-Scale unifies transcriptomic and textual data at unprecedented scales, surpassing both specialized single-cell models and general-purpose LLMs to provide a platform for next-generation single-cell analysis and the development of “virtual cells.”

A comprehensive differential diagnosis is a cornerstone of medical care that is often reached through an iterative process of interpretation that combines clinical history, physical examination, investigations and procedures. Interactive interfaces powered by large language models present new opportunities to assist and automate aspects of this process¹. Here we introduce the Articulate Medical Intelligence Explorer (AMIE), a large language model that is optimized for diagnostic reasoning, and evaluate its ability to generate a differential diagnosis alone or as an aid to clinicians. Twenty clinicians evaluated 302 challenging, real-world medical cases sourced from published case reports. Each case report was read by two clinicians, who were randomized to one of two assistive conditions: assistance from search engines and standard medical resources; or assistance from AMIE in addition to these tools. All clinicians provided a baseline, unassisted differential diagnosis prior to using the respective assistive tools. AMIE exhibited standalone performance that exceeded that of unassisted clinicians (top-10 accuracy 59.1% versus 33.6%, P = 0.04). Comparing the two assisted study arms, the differential diagnosis quality score was higher for clinicians assisted by AMIE (top-10 accuracy 51.7%) compared with clinicians without its assistance (36.1%; McNemar’s test: 45.7, P < 0.01) and clinicians with search (44.4%; McNemar’s test: 4.75, P = 0.03). Further, clinicians assisted by AMIE arrived at more comprehensive differential lists than those without assistance from AMIE. Our study suggests that AMIE has potential to improve clinicians’ diagnostic reasoning and accuracy in challenging cases, meriting further real-world evaluation for its ability to empower physicians and widen patients’ access to specialist-level expertise.

At the heart of medicine lies physician–patient dialogue, where skillful history-taking enables effective diagnosis, management and enduring trust^1,2. Artificial intelligence (AI) systems capable of diagnostic dialogue could increase accessibility and quality of care. However, approximating clinicians’ expertise is an outstanding challenge. Here we introduce AMIE (Articulate Medical Intelligence Explorer), a large language model (LLM)-based AI system optimized for diagnostic dialogue. AMIE uses a self-play-based³ simulated environment with automated feedback for scaling learning across disease conditions, specialties and contexts. We designed a framework for evaluating clinically meaningful axes of performance, including history-taking, diagnostic accuracy, management, communication skills and empathy. We compared AMIE’s performance to that of primary care physicians in a randomized, double-blind crossover study of text-based consultations with validated patient-actors similar to objective structured clinical examination^4,5. The study included 159 case scenarios from providers in Canada, the United Kingdom and India, 20 primary care physicians compared to AMIE, and evaluations by specialist physicians and patient-actors. AMIE demonstrated greater diagnostic accuracy and superior performance on 30 out of 32 axes according to the specialist physicians and 25 out of 26 axes according to the patient-actors. Our research has several limitations and should be interpreted with caution. Clinicians used synchronous text chat, which permits large-scale LLM–patient interactions, but this is unfamiliar in 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.

Large language models (LLMs) have shown promise in medical question answering, with Med-PaLM being the first to exceed a ‘passing’ score in United States Medical Licensing Examination style questions. However, challenges remain in long-form medical question answering and handling real-world workflows. Here, we present Med-PaLM 2, which bridges these gaps with a combination of base LLM improvements, medical domain fine-tuning and new strategies for improving reasoning and grounding through ensemble refinement and chain of retrieval. Med-PaLM 2 scores up to 86.5% on the MedQA dataset, improving upon Med-PaLM by over 19%, and demonstrates dramatic performance increases across MedMCQA, PubMedQA and MMLU clinical topics datasets. Our detailed human evaluations framework shows that physicians prefer Med-PaLM 2 answers to those from other physicians on eight of nine clinical axes. Med-PaLM 2 also demonstrates significant improvements over its predecessor across all evaluation metrics, particularly on new adversarial datasets designed to probe LLM limitations (P < 0.001). In a pilot study using real-world medical questions, specialists preferred Med-PaLM 2 answers to generalist physician answers 65% of the time. While specialist answers were still preferred overall, both specialists and generalists rated Med-PaLM 2 to be as safe as physician answers, demonstrating its growing potential in real-world medical applications.

Automated radiology report generation has the potential to improve patient care and reduce the workload of radiologists. However, the path toward real-world adoption has been stymied by the challenge of evaluating the clinical quality of artificial intelligence (AI)-generated reports. We build a state-of-the-art report generation system for chest radiographs, called Flamingo-CXR, and perform an expert evaluation of AI-generated reports by engaging a panel of board-certified radiologists. We observe a wide distribution of preferences across the panel and across clinical settings, with 56.1% of Flamingo-CXR intensive care reports evaluated to be preferable or equivalent to clinician reports, by half or more of the panel, rising to 77.7% for in/outpatient X-rays overall and to 94% for the subset of cases with no pertinent abnormal findings. Errors were observed in human-written reports and Flamingo-CXR reports, with 24.8% of in/outpatient cases containing clinically significant errors in both report types, 22.8% in Flamingo-CXR reports only and 14.0% in human reports only. For reports that contain errors we develop an assistive setting, a demonstration of clinician–AI collaboration for radiology report composition, indicating new possibilities for potential clinical utility.

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.

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.