The Song of the Cell: An Exploration of Medicine and the New Human

by Siddhartha Mukherjee

We—you and me—inhabit a second branch, or domain, called eukaryotes. The word eukaryote is a technicality: it refers to the idea that our cells, and the cells of animals, fungi, and plants, contain a special structure called a nucleus (karyon, or “kernel,” in Greek). This nucleus, as we will soon learn, is a storage site for chromosomes. Bacteria lack nuclei and are called prokaryotes—that is, “before nuclei.”

archaea look like bacteria, for the most part. They are tiny and lack some of the structures associated with animal and plant cells. But they are indisputably different from bacteria, or from plant, animal, and fungal cells. In fact, we still know relatively little about them.

New evidence suggests that this “modern” eukaryotic cell arose within archaea. In other words, life has only two principal domains—bacteria and archaea—and eukaryotes (“our” cells) represent a relatively recent sub-branch of archaea.

Vaccination, more than any other form of medical intervention—more than antibiotics, or heart surgery, or any new drug—changed the face of human health. (A close contender might be safe childbirth.)

In short, individual finches, like individual cells, don’t have an infinite repertoire or cosmos of beaks and happen to choose or adapt the one that is best suited to its circumstances. Rather, natural selection chooses the individual finch that happens to have an ideal beak for the natural disaster. The population of such selected finches grows. And the memory of the previous disaster persists.

Burnet likened them to “holes” in immune reactivity. It is one of the philosophical enigmas of immunity that the self exists largely in the negative—as holes in the recognition of the foreign. The self is defined, in part, by what is forbidden to attack it. Biologically speaking, the self is demarcated not by what is asserted but by what is invisible: it is what the immune system cannot see.

One critical feature of this form of communication is that the synapse has the capacity not just to excite the neuron to fire—as in the example above—but it can also be an inhibitory synapse, making the next neuron less prone to excitation. A single neuron can thus have positive inputs and negative inputs from other neurons. Its job is to “integrate” these inputs. It is the integrated total of these excitatory and inhibitory inputs that determines whether a neuron will fire or not.

This fetal warm-up act—the soldering of neural connections before the eyes actually function—is crucial to the performance of the visual system. The world has to be dreamed before it is seen.

you take your own cell—a skin fibroblast, or a cell from your blood—and you make it crawl backward in time and transform it into an iPS cell. And from that iPS cell, you can now make any cell you’d like—cartilage, neurons, T cells, pancreatic beta cells—and they’d still be your own. There would be no problem with histocompatibility. No immune suppression. No reason to worry about the guest turning immunologically against the host. And in principle, you could repeat the process infinitely—iPS into beta cell back to iPS cell into beta cell (to be fair, no one has tried this yet). The recursiveness, though, sets up yet another fantasy of a new human: one in whom every degenerated organ, or tissue, could be regenerated, and regenerated again, ad infinitum.

There are mysteries beyond mysteries. Engineered T cells are potently active against leukemias and lymphomas, but fail against ovarian and breast cancer. Why? The kind of immunotherapy used in Sam’s case eliminated the tumors in his skin, but not in his lungs. Why? As one of my own postdoctoral researchers discovered, our method of insulin depletion, via diet, decelerated endometrial and pancreatic cancers but accelerated the development of some leukemias in mice. Why? We don’t know what we don’t know.

neural organoids—tiny clusters of neuronal cells that, cultured in a matrix-like solution in the lab, organize themselves into ball-like shapes. Researchers had started calling them “mini-brains”—an exaggeration, no doubt—but there was something undeniably creepy about watching tiny balls with human neurons firing and communicating with each other. Had a thought, no matter how garbled, ever fired within one such organelle? If we poked them, did they feel sensation?