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January 30 - May 6, 2023
The deft management of Emily’s condition—and her startling recovery—saved the field of cell therapy. Emily Whitehead remains in that deep remission to this day. No cancer is detectable in her marrow or her blood. She is considered cured.
The transformation of medicine made possible by our new understanding of cell biology can be broadly divided into four categories. The first is the use of drugs, chemical substances, or physical stimulation to alter the properties of cells—their interactions with one another, their intercommunication, and their behavior. Antibiotics against germs, chemotherapy and immunotherapy for cancer, and the stimulation of neurons with electrodes to modulate
In 2010, when Emily Whitehead received her infusion of CAR (chimeric antigen receptor) T cells, or twelve years later, when the first patients with sickle cell anemia are surviving, disease-free, with gene-modified blood stem cells, we are transitioning from the century of the gene to a contiguous, overlapping century of the cell.
Life’s definition, as it stands now, is akin to a menu. It is not one thing but a series of things, a set of behaviors, a series of processes, not a single property.
Yes
It is difficult to imagine life without cells, just as it is impossible to imagine cells having no life.
Do crystals have cells? Dead people have cells; doesn't this make the claim that it's impossible to imagine cells without life circular? It's Impossible to imagine LIVING cells without life.
A cell brings materiality and physicality to a set of genes. A cell enlivens genes.
In humans and multicellular organisms, the process for the production of new cells to build organs and tissues is called mitosis—from mitos, the Greek word for “thread.” In contrast, the birth of new cells, sperm, and eggs for the purpose of reproduction—to make a new organism—is called meiosis, from meion, the Greek word for “lessening.”
The life cycle for a multicellular organism, in short, could be reconceived as a rather simple back-and-forth game between meiosis and mitosis.
Let us begin with a fact that is both strikingly self-evident to a cell therapist and startling to someone outside the field: in vitro fertilization (IVF) is cell therapy.
It has become so familiar, indeed, that we don’t even imagine it as cellular medicine, although, of course, it is precisely that: the therapeutic manipulation of human cells to ameliorate an ancient and aching form of human suffering: infertility.
It took almost a decade after the publication of “Early Stages of Fertilization” to convince the medical community that infertility was, in fact, a “disease.”
The fact that only about one-third of single-cell embryos form blastocysts reflects the one-third success rate of IVF that is found clinically. By playing the film backward, and using software to measure various parameters, the Stanford group identified just three factors that were predictive of future blastocyst formation: the duration of time that it takes the first cell to divide for the first time; the time between that first division and the second; and the synchronicity of the second and third mitosis.
By relying on this trio of parameters, the odds of predicting blastocyst formation (and, subsequently, the chance of viable implantation) increased to 93 percent.
The risk of HIV transmission from sperm, after the sperm has been washed for IVF processing, is zero.
Really? Or just remote, tiny.
But the gene edits that JK had obtained were not the same as the natural delta 32 mutation found in humans. He had produced a different mutation in the gene, possibly with the effect of conferring HIV resistance but possibly not—it’s impossible to know, since no one had performed such a gene edit before.
Wow.
Burnet extended the analogy to B cells. Imagine an enormous cohort of B cells in a body, each of which carries a unique receptor bound to its surface—each cell a finch with a unique beak, if you
She had internalized immunity.
Love his sense of humor.
he had perfected the English habit of deadly euphemism. If he thought an idea was stupid, or unscientific, he would look vaguely into the distance, pause, and say. “Oh! That notion seems… um… er… rather subtle.” At lab meetings, I must confess, I was often rather subtle.
the cells of the innate immune system—macrophages,
macrophages, neutrophils, and monocytes—are constantly surveying the body to find signs of injuries and infections.
Once phagocytosed, targeted to the lysosome and degraded, bacteria and viruses are chopped into peptides.
Unlike an antibody, a gunslinging sheriff itching for a showdown with a gang of molecular criminals in the center of town, a T cell is the gumshoe detective going door to door to look for perpetrators hiding inside.
Unlike the B cell, though, the T cell isn’t looking for a culprit to come bursting out of the saloon, guns a-blazing.
In short, H2 (or HLA) molecules serve two linked purposes. They present peptides to a T cell so that a T cell can detect infections and other invaders and mount an immune response. And they are also the determinants by which one person’s cells are distinguished from another person’s cells, thereby defining the boundaries of an organism.
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.
Wow
It is an unsolved quirk of the immune system that the cell type that confers active immunity and incites inflammation (the T cell) and the cell type that dampens these processes (the regulatory T cell) arise from the same parent cells: T cell precursors in the bone marrow.
Immunity and its opposite are twinned: the Cain of inflammation
conjoined with the Abel of tolerance.
the proteins that cancer cells make are, with a few exceptions, the same ones made by normal cells,
except cancer cells distort the function of these proteins and hijack the cells toward malignant growth. Cancer, in short, may be a rogue self—but it is, indubitably, a self.
Fundamental mysteries remained, of course. How this system achieved the acrobatic balancing act between generating a forceful immune response against pathogens, while ensuring that same response did not turn on our own bodies—how the Kampf against microbial invaders did not degenerate into the civil war of horror autotoxicus—was still somewhat of a profound riddle (in Sam P.’s case, we could never control the autoimmune hepatitis induced by the cancer-rejecting immunotherapy).
It was an infinitely strange feeling to hold an organ, about the size and shape of a large boxing glove, and imagine it as the repository of memory, of consciousness, of speech, temperament, sensation, and feeling. Love. Envy. Hatred. Compassion. All of these had reposed in some tangle of neurons. I was holding him, I thought, this man whose name, or identity, I would never know. Somewhere within that organ lived the neurons that had
once remembered his mother’s face. Somewhere was the memory of his last moment before the car had hurtled off the road, somewhere the melody of his favorite song.
Is this right? Or is only the living brain that has these?
