the complexity of cells -- 11/30/22

Today's selection -- from The Next 500 Years: Engineering Life to Reach New Worlds by Christopher E. Mason. The human body has about 30 trillion human cells plus another 30-40 trillion bacterial cells:
"Every multicellular organism begins as one cell, which contains all of the intricate instructions to synthesize, organize, and regulate not only this cell but the development and maintenance of all cells that will inevitably comprise the organism. All of these instructions are encoded in the first cell's DNA. This underscores the complexity of the genome and how each cell's expression must be controlled in specific ways depending on its function. The cells hailing from each tissue in the human body (e.g., muscle, lung, heart, liver) harbor a unique epigen­etic signature, which enables the maintenance of tissue-specific func­tions through the control of gene regulation, as just discussed.

"Our knowledge of the total number of unique cells, or cell types, is still growing. Previous estimates put the number of unique cell types in the human body at ~300, but new estimates from the Human Cell Atlas have shown that we may have thousands of cell types and subtypes, each harboring a unique function for a specific physiological state or response to stimuli. But even cells of the same cell type will not be identical. A cell's 'presentation' of molecules on their surface can radi­cally change depending on internal variables such as genetic mutations or altered states of their epigenome, transcriptome, and proteome, as well as external stimuli including drugs and interactions with other cells. This novel presentation is most pronounced with a neoantigen, when a cancer cell creates an entirely new molecule on the surface of a cell. Given its unique presentation, which wouldn't be found in nor­mal cells, this offers a unique target for safer cancer therapies.

The structure of the DNA double helix.

"The human body has about 30 trillion human cells plus another 30-40 trillion bacterial cells, for a total of about 70 trillion cells. If your body were a democracy, the human cells would often be the minority or equal party. You (as a human) would never win an election. Your loss of control would likely result in you rolling around in the soil or lying in a bathtub full of yogurt, which I do sometimes on Sundays. Regard­less of how you spend your Sundays, there are a lot of microbes in, on, and around your body. There are in fact so many microbes that they compose the bulk of the cells on Earth. This is a humbling and exciting statistic, and one which is vividly apparent for anyone who has ever had explosive diarrhea.

"While bacterial genomes are smaller in size (2-10 megabases vs. 3.1 gigabases for human), their biochemical activity is as important as, and sometimes more important than, the human component. Estimates by Lee Hood showed that 36 percent of the small molecules in the human body are either made by, or processed by, the microbiome. And about 25 percent of drugs that are designed for human disease can also affect the growth and biology of the body's microbial cells. As such, a treat­ment for a disease is never a treatment for one person; rather, it is a treatment for all cells across all kingdoms/domains of life.

"Yet this is only one facet within the large complexity in studying dis­ease and predicting treatment response. Our continual understanding of the true complexity of biology has enabled predictive modeling and patient-specific customized therapies as the new medical paradigm. Centers for 'precision medicine' and 'personalized medicine"' have become common at hospitals and medical centers around the world, with the goal to deliver the right treatment, to the right patient, at the right dose, and at the right time. Precision medicine has led to extraor­dinary breakthroughs in customized treatments for cancer, especially leukemia and lung cancers, where the 'Achilles' heel' of the cancer can be found and exploited, such that it will kill only the cancerous cells and leave the nonmalignant cells alone. Also, work in infectious disease and 'metagenomics,' or all DNA regardless of species, has enabled 'precision metagenomics,"' which can enable patient-specific antibiotic matching, or the discovery of mysterious species involved in the patient's disease, from which we can continually learn. Work in metagenomics has also led to unintended discoveries of microbes within tumors that possess an ability to process and metabolize che­motherapeutic agents and lead to resistance to therapy. Thus, some tumors may need to be treated first with antibiotics to kill the bacterial cells, and only then can the tumor cells be targeted. These treatment regimens represent a complete shift in medical treatment from preced­ing years and a new view of 'cross-kingdom biology' for medicine. To be a good human geneticist today, you must look beyond human DNA, since cells from all kingdoms of life and DNA from all nonhuman cells can influence every human."



Christopher E. Mason 


The Next 500 Years: Engineering Life to Reach New Worlds


The MIT Press


2021 by Christopher E. Mason


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