discovery of stem cells -- 3/1/23

Today's selection -- from The Song of the Cell by Siddhartha Mukherjee. The discovery of stem cells:
"On August 6, 1945, at about eight fifteen in the morning, thirty-one ­thousand feet above the Japanese city of Hiroshima, an atomic bomb nick­named Little Boy was dropped from an American military aircraft, a B-29 bomber nicknamed the Enola Gay. The bomb took about forty-five seconds to descend, and then detonated in midair, nineteen hundred feet above the Shima Surgical Hospital, where nurses and doctors were at work, and pa­tients still in their beds. It released about the energetic equivalent of fifteen kilotons of TNT -- about thirty-five thousand car bombs going off at once. A circle of fire, more than four miles in radius, spread out from the epicenter, destroying everything in its wake. The tar on the streets boiled. Glass flowed like liquid. Houses were flicked into oblivion, as if by a giant, incinerating hand. Outside the stone steps of Sumitomo bank, a man or woman who was vaporized instantly left a shadow of herself on the stone that had been blistered white by the conflagration.

"The waves of death that followed had three crests. About seventy thousand to eighty thousand people -- nearly 30 percent of the city's population -- were broiled to death almost instantly. 'I was trying to describe the mushroom [cloud], this turbulent mass,' one of the tail gunners of the aircraft wrote: 'I saw fires springing up in different places, like flames shooting up on a bed of coals [ ... ]  it looked like lava or molasses covering the whole city, and it seemed to flow outward into the foothills where the little valleys would come into the plain, with fires starting up all over.'

"Then came a second wave -- from radiation sickness (or 'atomic bomb sickness' as it was initially called). As the psychiatrist Robert Jay Lifton said, 'Survivors began to notice in themselves a strange form of illness. It consisted of nausea, vomiting, and loss of appetite; diarrhea with amounts of blood in the stools; fever and weakness; purple spots on various parts of body from bleeding into the skin ... inflammation and ulceration of the mouth, throat, and gums.'

"But there was yet a third wave of devastation to come. Survivors who received the lowest doses of radiation began to develop bone marrow failure, resulting in chronic anemias. Their white cell counts sputtered, then declined and collapsed over a few months. As the scientists Irving Weiss­man and  Judith Shizuru put it, 'those who died from the lowest lethal dose irradiation almost certainly died of hematopoietic [blood production] failure.' It wasn't the acute death of blood cells that killed these survivors. It was the inability to sustain the constant replenishment of blood; a collapse homeostasis of blood. The balance between regeneration and death had tipped. To paraphrase Bob Dylan: the cells not busy being born were dying.

"Macabre as it was, the bombing of Hiroshima provided proof that the human body possesses cells that continuously generate blood, not just in the moment, but for prolonged periods of time, through adulthood. If these cells are killed -- as they were in Hiroshima -- the entire blood system would eventually falter, unable to balance the rate of natural decay with the rate of rejuvenation. In time, these cells, capable of rejuvenating blood, would be termed 'blood-forming' -- or 'hematopoietic' -- 'stem and progenitor cells.'
"Our understanding of stem cells was born of a paradox: an unfathomably violent attack in an attempt to restore peace at the end of an unfathomably violent war. But stem cells are themselves a biological paradox. Their two principal functions seem, at face value, to be precisely opposed to each other. On one hand, a stem cell must generate functional 'differentiated' cells; a blood stem cell, for instance, must divide to give rise to the cells that form the mature elements of blood-white cells, red cells, platelets. But on the other hand, it must also divide to replenish itself -- i.e., a stem cell. If a stem cell achieved only the former function -- differentiation into mature, functional cells-the reservoir of replenishment would eventually be ex­hausted. Over the course of adulthood, our blood counts would keep falling year after year, until there were none left. In contrast, if it only achieved its own replenishment -- a phenomenon termed 'self-renewal' -- there would be no production of blood.
"It is the acrobatic balance between self-preservation and selflessness­ -- self-renewal and differentiation -- that makes the stem cell indispensable for an organism, and thereby enables the homeostasis of tissues such as blood. Cynthia Ozick, the essayist, once wrote that the ancients believed that the moist track of slime left behind by a snail in its trail was part of the snail's self. Bit by bit, as the slime rubs off, the snail is depleted, until the organism disappears altogether. A stem cell (or in the snail's case, a slime-producing cell) is a mechanism to ensure that the moist track of slime -- i.e., new cells -- are generated constantly and that the snail does not rub itself into oblivion."



Siddhartha Mukherjee


The Song of the Cell




Copyright 2022 by Siddhartha Mukherjee, M.D.


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