Reprogramming immunity: Code that could save us | Gordon Broderick | TEDxUniversityofSaskatchewan

The Immune System as a Computer: A Journey from Apollo 8 to Personalized Medicine

Key Concepts:

• Genomic Computer: The concept of DNA functioning as a complex information processing system.
• Digital Twin: A virtual replica of a biological system (in this case, the immune system) used for simulation and prediction.
• Immune System as a Control System: The idea that the immune system operates like a sophisticated computer, processing information and executing programs.
• Autoimmune Illnesses: Conditions where the immune system attacks the body’s own tissues.
• Persistent Conditions (e.g., Long COVID, Gulf War Syndrome): Chronic illnesses characterized by lingering symptoms, potentially linked to immune system dysregulation.
• Molecular Recipe/Immune Operating System Update: A future vision of personalized medicine involving tailored interventions to optimize immune function.

The Genesis of an Idea: From Space Exploration to Biological Control

The speaker begins by recalling the Apollo 8 mission in 1968, highlighting the incredible precision of the navigation computer required for the journey to the moon. This sparked a childhood question: does the human body possess a similar control system? This initial curiosity mirrored the burgeoning research of scientist Stuart Kaufman, who questioned whether cells themselves had internal control circuitry. Eric Davidson at Caltech further formalized this idea by coining the term “genomic computer” to describe DNA, attracting engineers and physicists to the field of biology, viewing it as a programmable system. The core question evolved: if a single cell functions like a computer, what capabilities emerge when millions of cells interact – could they form a “thinking machine”?

The Immune System: A Complex Computational Network

The focus narrows to the immune system, described as a “rag tag pack of cells” that defend the body against infection and injury. These cells aren’t random actors; they operate according to a “game plan” – a program – coordinating actions and learning from experience, even exhibiting memory. The speaker draws an analogy between immune cells and computer processors, constantly running programs like “fight infection,” “heal wounds,” and “clean up damaged cells.” While typically functioning flawlessly, the immune system can “misread the room” and initiate inappropriate responses, leading to autoimmune diseases. The speaker cites statistics indicating that approximately 1 in 15 men and 1 in 7.5 women will develop an autoimmune illness during their lifetime. Furthermore, conditions like Long COVID and Gulf War Syndrome demonstrate the potential for the immune system to become “stuck” in a dysfunctional state, affecting between 10-30% of those initially infected with COVID-19 and impacting tens of thousands of veterans respectively.

The “Blue Screen of Death” and the Need for a Reboot

The speaker likens immune system dysfunction to a computer freezing, referencing the infamous “Microsoft blue screen of death.” The question then becomes: can the immune system be “rebooted”? Driven by this question, the speaker and their team utilized advanced tools like flow cytometers, mass spectrometers, and immunoassays to analyze immune cell activity. Initial investigations focused on individuals with persistent symptoms, attempting to understand the underlying mechanisms of their condition. They employed exercise as a controlled stressor, observing that patients exhibited prolonged inflammatory responses – a “smoke detector blaring” even after the stimulus was removed – suggesting the immune system was trapped in a perpetual emergency response.

Building a Digital Twin of the Immune System

Recognizing the complexity of the immune system, the team embarked on a decade-long project to create a “digital twin” – a virtual replica of the immune system. This involved compiling data from tens of thousands of research papers, writing extensive code, and leveraging powerful computing resources. The digital twin was initially tested by simulating a viral infection and exposure to various chemicals. Remarkably, the digital twin replicated the molecular signatures observed in both patients with persistent symptoms and healthy individuals. This validation provided a crucial understanding of the biological processes underlying these illnesses and why recovery often stalls.

Drug Repurposing and the Power of Sequential Therapy

The next step involved testing potential treatments within the digital twin. The team virtually screened thousands of FDA-approved drugs, individually and in combination. Interestingly, no single drug proved effective on its own. However, a specific sequence of two drugs – an anti-inflammatory followed by a hormone regulator – successfully “rescued” up to 70% of the digital patients. This suggested that calming the initial inflammatory response followed by hormonal modulation could effectively “reset” the immune system.

Validation and Clinical Translation: From Mouse Models to Human Trials

To validate the digital twin’s predictions, the team tested the drug sequence in an animal model mimicking Gulf War Syndrome. Administering the drugs in the incorrect order yielded no effect, but following the sequence predicted by the digital twin resulted in recovery. This success led to human clinical trials, offering hope to families who had been struggling with these conditions for decades.

The Future of Personalized Immunotherapy

The speaker concludes by outlining ongoing research at the University of Saskatchewan’s Vaccine and Infectious Disease Organization (VIDO). The team is building increasingly sophisticated digital twins, incorporating more proteins, cells, and interactions, and utilizing artificial intelligence and quantum computing to fill in knowledge gaps. The ultimate vision is a future where doctors prescribe “molecular recipes” – personalized updates to the immune “operating system” – tailored to each patient’s unique needs. This represents a full-circle moment for the speaker, realizing a childhood curiosity about the body’s control systems and contributing to the development of personalized immunotherapy.