Our Immune Memory Contains a Detailed History of Exposures but We Can’t Read It

Conduct a large-scale, comprehensive study to establish causal links between persistent microbial/viral infections (such as herpes simplex 1) and neurodegenerative diseases like Alzheimer’s Disease. Such a study would illuminate the role of infections in increasing disease risk and progression. This effort could serve as a sequel to the Genome-Wide Association Studies (GWAS) that have been performed since the completion of the Human Genome Project. Many diseases failed to show obvious genetic etiologies from those GWAS efforts, suggesting a role for the environment in disease causation. Large-scale infection profiling could therefore unearth etiologies that were not possible to detect by GWAS.

Adapt and build experimental and computational methods to read out distributed and sparse immune memory signatures from adaptive immune cells. Beyond individual antibody-antigen binding, this approach focuses on signatures distributed across cellular subpopulations and the repertoire. Decoding these signatures could identify hidden causes of and cures for disease, enabling more accurate diagnosis, treatment, and prevention of chronic conditions.

We need a way to programmably induce immune tolerance to a user-defined foreign protein, in order to enable many new forms of gene and cell therapy (not to mention help with autoimmune diseases). This is especially needed for brain computer interface as many of the most powerful concepts for BCI would involve adding foreign protein such as transducer proteins for optical or acoustic signals. As Hannu Rajaniemi wrote, “a flexible ability to induce immune tolerance to opsins is a prerequisite of a two-way mind meld with computers”.

Generate longitudinal, multi-omic immunological data from a diverse cohort of individuals. This dataset would be critical for enabling immune-ome modeling and prediction (for example, in forecasting vaccine responses).

Develop a universal immune-computer interface to enhance the immune system’s targeting of pathogens and cancers, while reducing issues such as autoimmunity and transplant rejection. The ICI would involve two-way coupling—where the immune system and computer mutually optimize their matching processes—and real-time feedback loops. An example could be a wearable device that integrates mRNA manufacturing with single-cell sequencing.