Design Principles of Life, Disease, and Aging

# A periodic table of diseases *Evidence guide: Teaching analogy and systems-medicine hypothesis. Categories and predicted disease risks belong to a working framework.* Alon proposes a periodic table of diseases as a metaphor. It is a conceptual systems-medicine framework, which he describes as a working draft. It is not a clinical classification, and it does not replace standard medical systems such as the international disease codes. Here, each element is a cell type. The rows go by how many cells of that type the body has, from about a hundred million, like the parathyroid, to trillions, like skin cells. The columns go by turnover: from permanent cells such as neurons, which are not replaced, to barrier tissues such as skin and gut, which renew within days to weeks. In Alon's lecture version, there are four broad columns: permanent tissues, front-line tissues, protected secretory tissues, and barrier tissues. Each column tends to have its own class of disease, which the framework traces back to a circuit. Permanent tissues, like neurons, skeletal muscle, bone and the lens of the eye, are not replaced, but they are continually maintained. With age, damage production rises while maintenance saturates. Their typical diseases are degenerative: Alzheimer's disease, osteoporosis, sarcopenia and cataract. Front-line tissues, like the lung's air sacs, cannot hide their stem cells from damage. In the model, if stem-cell removal outpaces their proliferation, the tissue can collapse locally. The proposed disease class is progressive fibrosis of old age, such as idiopathic pulmonary fibrosis, and, in the framework, osteoarthritis. The secretory column shows three zones by cell number, all linked to the secrete-and-grow circuit and to the fact that cells mutate. Tiny glands, under about a gram, rarely get autoimmune disease but get toxic adenomas, benign tumors that over-secrete. Glands of about one to ten grams get organ-specific autoimmune disease, like type-one diabetes and Hashimoto's thyroiditis. Above about ten grams, cancer becomes the most prevalent disease. The proposed logic: few cells means few dangerous mutants, so surveillance is not worth it. More cells call for immune surveillance, at the cost of autoimmunity. Even more cells shift toward stem-cell designs, which carry cancer risk. Barrier tissues, such as the skin, gut and airways, have the fastest turnover and constant contact with the outside world. They show immune hypersensitivity diseases, such as psoriasis, asthma and inflammatory bowel disease, often starting young, and many common cancers. Like Mendeleev's gaps, the table suggests predictions. A secretory cell type of about one to ten grams should carry a risk of autoimmune disease, and a tiny secretory cell type a risk of toxic adenoma. The framework proposes candidates that remain to be tested. Some diseases, such as systemic autoimmune diseases and psychiatric disorders, do not fit easily. The table includes only some cell types and the most prevalent diseases. Sources: [sysmed-notes](https://www.weizmann.ac.il/mcb/alon/courses/system-medicine-2022-2023), [lecture12](https://www.weizmann.ac.il/mcb/alon/sites/mcb.UriAlon/files/uploads/lecture_12_periodic_table_july12c.pdf), [katzir2021](https://doi.org/10.1111/acel.13314), [korem2020](https://doi.org/10.1016/j.immuni.2020.04.022).