Stem cell

Stem cells weren't invented—they were discovered by accident when conditions aligned to make the invisible visible. Ernest McCulloch and James Till at the University of Toronto were studying radiation damage in mice in 1961, injecting bone marrow cells into irradiated animals, when they noticed lumps in the spleens. Each lump turned out to be a colony of cells descended from a single progenitor—a cell that could both self-renew and differentiate into specialized types. The discovery emerged because atomic bomb research had created expertise in radiation biology, cell culture techniques had matured enough to grow colonies, and blood genetic markers could prove that colonies came from donor cells, not host survivors. The insight wasn't that stem cells existed—Russian scientist A.A. Maximov had proposed the concept in 1909—but that they could be identified, counted, and studied as discrete biological entities.

Their 1961 paper in Radiation Research established the colony-forming assay, and their subsequent work with Siminovitch defined the key properties: self-renewal and differentiation. A stem cell divides to produce both another stem cell and a specialized cell, maintaining a reservoir while generating function. The physics were cellular, not molecular.

Earlier researchers had theorized about blood-forming cells, but without a way to visualize individual cells creating colonies, the concept remained abstract. The spleen colony assay made stem cells concrete—you could inject a known number of bone marrow cells, irradiate the recipient to eliminate its own stem cells, wait ten days, and count colonies. Linear proportionality proved each colony originated from one cell. That quantification transformed stem cells from hypothesis to measurable reality.

That Alexander Friedenstein in Moscow independently discovered mesenchymal stem cells in the mid-1960s—bone marrow cells that could differentiate into bone, cartilage, and fat rather than blood—proves the conditions had aligned globally. Both McCulloch-Till and Friedenstein used radiation to clear space for transplanted cells, both relied on colony-forming assays, and both operated in Cold War contexts where radiation biology received military funding. The convergent discovery wasn't collaboration; it was parallel problem-solving. Maximov's 1909 stem cell concept had waited fifty years for the tools to make it testable.

When those tools arrived—radiation biology expertise from weapons research, tissue culture from cancer studies, genetic markers from immunology—multiple labs found stem cells because the adjacent possible had opened. This pattern repeats throughout biology and business: the first application shapes the ecosystem.

Path dependence locked in through the bone marrow transplant infrastructure. The cascade McCulloch and Till unleashed took decades to fully materialize. Their work refined bone marrow transplantation, which had begun in 1957 before anyone knew what stem cells were. The first successful sibling donor transplant occurred in 1968, enabled by human leukocyte antigen (HLA) typing developed in the mid-1960s. But the real explosion came in 2006 when Shinya Yamanaka created induced pluripotent stem cells (iPSCs)—adult cells reprogrammed to stem cell state using just four genes. Induced pluripotent stem cells avoided the ethical controversies of embryonic stem cells while providing patient-specific cells for therapy.

By 2025, regulatory bodies globally had approved 115 clinical trials testing human pluripotent stem cell (hPSC)-based treatments for retinal diseases, Type 1 diabetes, Parkinson's, heart failure, and spinal cord injuries. Chimeric antigen receptor T-cell (CAR-T) therapies—engineering a patient's stem cells to attack cancer—moved from experimental to standard care for certain blood cancers. In 2025, the FDA granted FT819—an off-the-shelf CAR-T therapy for lupus—Regenerative Medicine Advanced Therapy designation, fast-tracking development while Phase 1 trials demonstrated durable drug-free remission in early patients.

Niche construction accelerated as stem cell knowledge created new research fields. Tissue engineering emerged to build scaffolds for stem cells to colonize. 3D bioprinting positioned stem cells as living ink. Gene therapy used stem cells as delivery vehicles—edit the genes in a patient's blood stem cells, transplant them back, and the corrected cells repopulate the marrow permanently.

A 2025 nitric oxide-infused hydrogel demonstrated how materials science now designs environments to keep transplanted stem cells alive in damaged tissue. Each advance required stem cells as foundation—you can't engineer tissues without understanding what makes cells specialize, and you can't do gene therapy on blood without knowing which cells to target.

Hospitals built transplant units, physicians specialized in conditioning regimens, and HLA typing labs became essential. The 1963 discovery had assumed stem cells meant blood stem cells, focusing research on hematopoietic applications for decades. When other stem cell types emerged—neural, mesenchymal, cardiac—they inherited the bone marrow paradigm: isolate, expand, transplant. Alternative approaches—activating resident stem cells in situ rather than transplanting external ones—struggled for funding because the transplant model was already proven.

By 2025, stem cell research faces its own punctuated equilibrium. iPSCs promised personalized regenerative medicine, but manufacturing patient-specific cells costs too much for most applications. Off-the-shelf allogeneic stem cells—grown from universal donors—now dominate clinical trials, accepting immunosuppression risks for manufacturing economies. Stem cells didn't just enable new therapies; they forced medicine to confront industrialization. The cells McCulloch and Till counted in mouse spleens in 1961 now require bioreactors, clean rooms, and supply chains. The discovery that made cells visible also made them manufacturable—and manufacturing doesn't care about the elegance of self-renewal, only whether you can make a billion doses that work. The next punctuated equilibrium won't come from understanding stem cells better. It will come from making them cheaper.