CZI Sets Four Scientific Grand Challenges to Transform Human Health at the Intersection of AI and Biology

Since our beginning, CZI has been bold in its thinking and ambition. We set an audacious mission to advance the science and technology that will make it possible to cure, prevent and manage all disease by the end of this century. We’ve made big bets along the way — bets that are paying off and showing real progress.

A fundamental challenge confronting the scientific community is a limited understanding of the unique role, function, and behavior of each individual cell within the human body. As the basic building blocks of life, cells perform sophisticated processes, adapt to genetic and environmental variations, and self-organize into intricate tissues and organs. Greater insight into how each distinct cell operates within our bodies will transform human health.

Through our work, it’s now possible to visualize how cells are damaged by disease using an imaging technique enabled by the world’s most powerful X-rays. By building software for scientists, we changed how biologists analyze cells to find insights into health and disease, and we are building a landmark single-cell dataset of one billion cells to train AI models to advance understanding of cellular behavior and gene function. We created the first worldwide patient-driven research network developing treatments and cures for rare diseases, and we’ve accelerated how research is shared through our support for preprints and open science so scientists can more quickly build upon each other’s work. We developed the first sensor capable of monitoring inflammation in real time, and we funded and built the largest AI computing system for nonprofit life sciences research.

Building on this work, CZI has identified four scientific grand challenges, each focused on solving key biological questions that will demystify the inner workings of human biology to produce breakthroughs and accelerate science to significantly decrease the burden of human disease.

• Build an AI-based virtual cell model to predict and understand cellular behavior
• Develop novel imaging technologies to map, measure and model complex biological systems
• Create new tools for sensing and directly measuring inflammation within tissues in real time
• Harness the immune system for early detection, prevention and treatment of disease

To lead these challenges, we’re building a leadership team of some of the foremost experts across biology, engineering, technology and innovation. Scott Fraser, president of the Chan Zuckerberg Institute for Advanced Biological Imaging, leads our scientific challenge in imaging. Later this year, our Chan Zuckerberg Biohub San Francisco and Imaging Institute will join together, with Scott as head of the newly formed organization. Andrea Califano, president of our Chan Zuckerberg Biohub New York, leads the challenge to harness the immune system for early detection, prevention and treatment of disease, and Shana Kelley, president of our Chan Zuckerberg Biohub Chicago, leads the challenge to create new tools for sensing and directly measuring inflammation within tissues in real time. We will further build out this team with a head of AI who will lead the challenge to build an AI-based virtual cell model, as well as a head of data.

A new era of discovery

We are at a pivotal moment in science where the intersection of artificial intelligence and biology has the potential to transform how biological research is done. We saw this moment coming and have been working for nearly a decade to build the tools and generate the data sets that are providing the foundation for machine learning to help power this next leap in our understanding of human health and disease.

Over the next ten years, we will pursue these grand challenges with great rigor, speed and intensity. We are uniquely positioned to do this work, by bringing together scientists, engineers, and AI and machine learning experts to solve complex challenges in human biology. We’ve invested resources into creating cross-disciplinary research institutes — Biohubs — which partner with some of the world’s best universities on significant challenges in biology and health. We built a science technology team that develops models, methods, tools and datasets to help researchers come to meaningful conclusions about human health and disease. And, we funded research in more than 30 countries globally to accelerate science in pursuit of our mission. This powerful, distinct combination will move us faster toward our mission.

In the near future, we see a world where biologists use AI-powered simulations to model the intricate transitions from healthy to diseased cellular states; technologies that track the development journey of every cell in an organism with molecular-level resolution, making visible what was once invisible; and tools that harness the immune system to detect inflammation, cancer, and other conditions early enough to prevent disease before it even begins.

By creating and giving scientists new tools and technology capable of revealing the precise inner workings of human biology, scientists will have the tools to cure, prevent and manage disease in this century.

Build an AI-based virtual cell model to predict and understand the behavior of cells

To truly grasp how a cell operates, researchers at CZI will generate large datasets and use AI tools to create powerful models for predicting and designing cellular behavior. AI and virtual cell models will help scientists understand the underpinnings of human health and disease, which in turn can speed up the development of drugs, diagnostics and other therapies. These models will be openly shared and boast intuitive interfaces so that biologists around the world can use these resources to accelerate their own research and better understand disease from the moment it begins in a cell.

Develop novel imaging technologies to map, measure and model complex biological systems

Current imaging technologies do not give a complete picture of how complex biological systems, such as the immune system, function or fail. Teams at CZI’s San Francisco Biohub and Imaging Institute are leading the development of breakthrough imaging technologies to capture biological processes across scales — from individual proteins to whole organisms. These new capabilities will help train and validate virtual cell models and reveal organizing principles for how cells form into specific tissues and organs, enabling more effective treatments for conditions affecting millions of people worldwide.

“If successful, we will develop and deploy imaging tools that put imaging on par with, or even ahead of, the genome-wide data collection approaches that have driven modern biology forward.” – Scott Fraser, President, CZ Imaging Institute

Create new tools for sensing and directly measuring inflammation within tissues in real time

Inflammation is a key driver of over 50% of deadly diseases, including cancer and heart disease. It has been difficult to study using conventional approaches because of the complexity of interactions between the immune system and living tissues and cells. Using an engineering-driven approach, scientists at the Chicago Biohub are performing the first-ever comprehensive and direct measurements of inflammation in human tissues. The team is building tools to monitor immune cells within tissues in real time, and ultimately steer the immune system away from tipping points that lead to inflammatory disorders.

“Inflammation is a huge driver of human disease. If we could watch inflammation emerging in real time, and then have ways to turn it around, we are looking at a much lower burden of disease in the human population, and hundreds of millions of preventable deaths worldwide.” – Shana Kelley, President, CZ Biohub Chicago

Harness the immune system for early detection, prevention and treatment of disease

Diseases like Alzheimer’s or pancreatic cancer are almost invariably diagnosed when they have progressed to the stage that little can be done to cure them or even mitigate progression. Using AI and advanced bioengineering approaches, scientists at the New York Biohub are creating immune cells to detect diseases, report back on their characteristics, and then deliver therapeutics specifically to affected cells, avoiding adverse effects on the entire body. Just as precision-guided systems find their targets, we are enhancing the natural homing abilities of immune cells to detect signals generated by diseases they were not originally optimized to discover.

“Success is being able to detect malignancies, like pancreatic or ovarian cancers, when there is still plenty of time to cure them and also to replace therapies like chemo that cause so many side effects with therapies designed to cure individual cells, leaving the rest of our organs and body unharmed.” – Andrea Califano, President, CZ Biohub NY