First podcast! With 10x Genomics CEO Serge Saxonov

Spatial Perturb-seq, so hot right now! With Alexander Nevue

“It's one extra step ahead of a single cell RNA-seq workflow where we can get all the information that we can get from standard Perturb-seq, but we also know the spatial location.” That’s how my guest this week, Arc Institute Senior Scientist Alexander Nevue, describes PerturbSpace, a new method he and his colleagues introduced in a preprint posted to BioRxiv [https://www.biorxiv.org/content/10.64898/2026.05.25.727765v1] May 18.  PerturbSpace is the latest method to marry the power of CRISPR-based perturbation screening, where genes across the genome are systematically targeted and the effects of those perturbations are read out in the transcriptome of the cell in which they were made.  This juncture of CRISPR-based screening and spatial transcriptomics is one of the hottest areas in molecular biology right now, with nearly 10 different methods published in the last two years, from leading scientists including Genentech’s Aviv Regev; Harvard University’s Xiaowei Zhuang, the inventor of MERFISH and cofounder of Vizen; Yale University’s Rong Fan, and the Broad Institute’s Sami Farhi.  Join Alex and me as we discuss the PertubSpace workflow, its advantages and disadvantages compared to other spatial perturb-seq methods, and where he sees the data from these screens making the most impact.  Links to other publications of spatial perturbation screening methods with notable authors:  PerturbView. Aviv Regev and Erik Lubeck of Genentech. https://www.nature.com/articles/s41587-024-02391-0 [https://www.nature.com/articles/s41587-024-02391-0] Large-scale pooled in vivo CRISPR screening. Jonathan Weissman of MIT and Harvard’s Xiaowei Zhuang, inventor of MERFISH and cofounder of Vizgen. https://www.biorxiv.org/content/10.1101/2024.11.18.624217v3 [https://www.biorxiv.org/content/10.1101/2024.11.18.624217v3] SPAtial Cell Exploration (SPACE). Joe Beechem of Bruker/NanoString, in collaboration with Merck. https://www.biorxiv.org/content/10.1101/2025.09.14.675819v2 [https://www.biorxiv.org/content/10.1101/2025.09.14.675819v2] Perturb-DBiT. Rong Fan of Yale University, inventor of DBIT family of methods and cofounder of AtlasXOmics . https://www.researchsquare.com/article/rs-6481967/v1 [https://www.researchsquare.com/article/rs-6481967/v1] CRISPRMap. Jellert Gaublomme of Columbia University, Dan Landau of Weill Cornell Medicine. https://www.nature.com/articles/s41587-024-02386-x [https://www.nature.com/articles/s41587-024-02386-x] Perturb-FISH. Sami Farhi  of the Broad Institute.  https://www.cell.com/cell/fulltext/S0092-8674(25)00197-7 [https://www.cell.com/cell/fulltext/S0092-8674(25)00197-7] NIS-Seq Jonathan L. Schmid-Burgk of University Hospital Bonn. https://www.nature.com/articles/s41587-024-02516-5 [https://www.nature.com/articles/s41587-024-02516-5] Spatial Perturb-Sseq. Wei Leong Chew of A*STAR GIS. https://www.nature.com/articles/s41467-026-69677-6 [https://www.nature.com/articles/s41467-026-69677-6]

Remembering Craig Venter With Jamie Shreeve, Author of 'The Genome War'

Craig Venter, the renegade scientist who tried to beat the publicly-funded Human Genome Project with a private company — and nearly succeeded — died last week at 79. My guest this week, Jamie Shreeve, shadowed Venter for two years as part of his research for The Genome War, a book about the saga that captured not only the best and the worst aspects of Venter, but of human nature itself.  Shreeve and I evaluated Venter’s legacy while also reminiscing about the man who will be remembered both as a good friend and as an “asshole” in equal measure. We also remembered Venter’s longtime colleague and Nobel laureate Hamilton Smith, who died in October. Shreeve is also revealing, for the first time, a James Watson take on Venter so brutal that Shreeve left it out of the book.  I never met Venter, so my conception of him has always been and will forever be based on Shreeve’s portrait of him. The Genome War is one of my all-time favorite books and provides an even fuller picture. Please consider buying a copy through your local bookstore: https://bookshop.org/p/books/the-genome-war-how-craig-venter-tried-to-capture-the-code-of-life-and-save-the-world-james-shreeve/e018f9700a01fcd0?ean=9780345433749&next=t [https://bookshop.org/p/books/the-genome-war-how-craig-venter-tried-to-capture-the-code-of-life-and-save-the-world-james-shreeve/e018f9700a01fcd0?ean=9780345433749&next=t] Shreeve is also the author of The Neandertal Enigma [https://www.goodreads.com/book/show/19447625-the-neandertal-enigma] and co-author of Lucy’s Child: The Discovery of a Human Ancestor. A note: In the interview I say that sequencing-by-synthesis, the dominant method for analyzing whole human genomes today, is similar to the shotgun sequencing method used by Venter at Celera. As I was informed by Adam Phillippy, a leading computational biologist, this is not correct.  “Performing de novo genome assembly, as was required for the first genome project, is nearly impossible from short (~100 bp) reads,” he said in an email. “During the entire short-read era, people were mapping reads to the human reference, rather than re-assembling the genome each time.” Still, Venter's work helped push the field towards assembling a reference genome, which was essential for SBS. “This method of analysis was only possible because a reference sequence already existed,” Phillippy said. “Early SBS would have been nearly worthless without a reference sequence.”

AI Virtual Cell Pioneer Christina Theodoris

Do AI models in biology have to get bigger to get better? And what can you do with more training, more computing power, and more outputs?  Joining me this week to talk about MaxToki [https://www.biorxiv.org/content/10.64898/2026.03.30.715396v1], a new AI-powered model that can predict how cells age, is Christina Theodoris, a physician scientist at the Gladstone Institutes who is using her models to study cardiovascular disease. She's a pioneer in this field, having developed GeneFormer, a model trained on millions of single-cell transcriptomes that can predict what will happen when gene networks are disturbed. But size isn’t everything. “The biggest impact we see though is with diversity of the data,” she said. “As we increase the diversity, that actually has even more impact than just the pure numbers, let's say if you were to use cells that are similar to the ones seen before.” This has implications for training new, even more powerful models.  Theodoris is also an accomplished visual artist whose paintings draw on surrealism, cultural heritage, and memory.  In addition to her models, we talked about the trend of AI slop, how she would paint her models, and whether or not she likes the Ion Genomics logos I came up with.  To learn more about her art, please check out Christinatheodoris.com [http://Christinatheodoris.com] Links to Theodoris’ work discussed in this episode: MaxToki Preprint https://www.biorxiv.org/content/10.64898/2026.03.30.715396v1 [https://www.biorxiv.org/content/10.64898/2026.03.30.715396v1] Scaling GeneFormer “Scaling and quantization of large-scale foundation model enables resource-efficient predictions in network biology,” Nature Computational Science https://www.nature.com/articles/s43588-026-00972-4 [https://www.nature.com/articles/s43588-026-00972-4] "Discovery of candidate therapeutic targets with Geneformer," Nature Protocols https://www.nature.com/articles/s41596-026-01364-8 [https://www.nature.com/articles/s41596-026-01364-8]

First podcast! With 10x Genomics CEO Serge Saxonov

Earlier this week I spoke with 10x Genomics CEO and Cofounder Serge Saxonov at the AACR meeting, where 10x launched Atera, its new instrument for spatial biology. In addition to hitting product pricing and specs, we spoke about the challenges of starting a new company, our favorite model organisms, and why he thinks Atera will be 10x’s most consequential product launch yet.