Science1 publisher2 min readPublished
Since 1999, biologists have named about 20 new ways for a cell to die
One of them is alkaliptosis, in which a cell dies because its interior turns basic. The catalogue gives drug developers a menu of mechanisms to aim at. The evidence for choosing among them is still preclinical.
The Scientist · Science desk
What happened
- Cell biology long recognised two main deaths, accidental necrosis and the orderly, stepwise apoptosis, and since 1999 researchers have described about 20 further kinds.
- This spring, researchers studying flatworms added ruptosis, in which particular cells explode to splatter toxins over invading bacteria.
- Tang argues that the manner of death matters because dying cells release signals and material that act on neighbouring cells, shape tissue function and influence immune responses.
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Why it matters
- decision Tang says the work pointed to an entirely new way to kill cancer cells, so a preclinical program now has to answer which death it induces and why that one.
- constraint Some cells can delay their own death or pull back from the brink. A therapy that assumes one trigger finishes the job has to account for that.
- capability Blocking death becomes a drug goal alongside inducing it, with groups investigating rescue of dying cells in the heart and brain and the calming of inflammatory disease.
- precedent Hu credits gene editing, high-resolution imaging and omics tools for turning up the newer forms, so a pathway label attached to a program today can be redefined or subdivided before that program finishes.
Alkaliptosis came out of a process of elimination. Tang and his colleagues had dead cells and no cause, worked through several established death pathways, and cleared all of them [1]. The difference they eventually measured was pH: the cells had an unusually high internal pH, and being basic is what killed them [2]. The name came afterwards [3]. Tang did the studies at the University of Pittsburgh in Pennsylvania and now works at the University of Texas Southwestern Medical Center in Dallas [4].
Elimination is the usual route in this field, partly because the object of study removes itself. "If you have a successful cell-death experiment, your material disappears," said Scott Dixon, a cell biologist at Stanford University in California [8]. So a new pathway tends to be established the way Tang's was, by showing which known routes are not responsible [1].
Four of the roughly twenty post-1999 forms were defined in 2025 alone [10], about a fifth of the catalogue in a single year [22]. The entries have come unevenly. Across the whole period the average works out to one new named form roughly every 16 months [23].
The labels are not interchangeable at the tissue level. Apoptosis is orderly: the cell releases membrane blebs that the immune system can sweep away [7]. Pyroptosis is pro-inflammatory, necroptosis activates immune cells as it proceeds, and ferroptosis destroys membranes by way of iron [12]. On those descriptions, killing the same tumour cell through pyroptosis and killing it through apoptosis leave the surrounding tissue in different immune states [12].
Some of the newer causes are narrow and chemical. Researchers described death by excess copper in 2022 and death by sodium overload in 2025 [14]. Qing Zhong, a biochemist at Shanghai Jiaotong University School of Medicine who led the sodium work, says such findings reveal the limits of cellular survival [15].
Nature's feature is a survey of the biology and of applications under investigation [21]. It cites no trial in which choosing one death pathway over another improved a patient's outcome [24]. On this evidence, pathway selection is a preclinical design variable with a mechanistic case behind it. Attributing past oncology or autoimmune failures to the wrong choice would need outcome data the field has not published. "Cell death is not simply the end of a cell's life," Tang said [17].
What to watch
- Whether an alkaliptosis-inducing compound enters a registered trial with internal pH as a read-out.
- Whether 2026 adds named pathways at the 2025 rate, or newer entries get folded into existing ones.
- Whether ruptosis is found in animals other than flatworms.