I read in the New York Times recently that Beatrice Mintz had passed away at the age of 100. (Reading the Times obituaries is a practice that begins with receipt of your Medicare card; my friend Ari Goldman says you want to make sure your own name is not there.) She had been a cancer biologist for many years at Fox Chase Cancer Center in Philadelphia, but what I was reminded of was one particularly awesome series of experiments she conducted in 1968. I guess I was a freshman at Columbia then and mostly on strike. OK, everyone else was on strike—I was studying.

One possible, and perhaps the most important, way to think about cancer etiology is to think of it as an error in cellular differentiation, known as aberrant differentiation. Under normal circumstances during embryogenesis and development, primitive stem cells differentiate into the specialized cells in each of our organs—liver cells, neurons, breast cells, bone etc.—by turning on the appropriate genes that comprise the network for each of those specialized cells. There are sophisticated signaling systems in place to let each cell know which pathway it is fated to be on and how to differentiate, based in part on its location in the body. The theory of aberrant differentiation is that the genes for malignancy are contained in the genome, just as the genes for liver or neuron or kidney are contained in the genome, but the cancer differentiation pathway is suppressed and not turned on under normal circumstances. This malignancy pathway is triggered by something bad—perhaps a mutation or some other signal—and thus the cell differentiates inappropriately or aberrantly down the malignancy pathway into a cancer cell, just as it might differentiate into a liver cell.

Basically, this theory suggests that the malignancy genes sit dormant within each of our cells waiting to be activated. If one asks, why would evolution have retained this within our cells, one must believe that these genes have purposes that are critical to the cell under normal conditions of growth and development and thus are essential to the cell and are retained.

Which brings us to Beatrice Mintz. She was born in New York to Jewish parents from Galicia in 1921 and went to Hunter College, where she majored in biology. When it came time for graduate school, Beatrice was rejected by the elite Ivy League schools, presumably because of antisemitism and quotas, and perhaps also as my daughter Dana suggested because she was a woman, so she went to the University of Iowa for her PhD. Upon graduation, she joined the faculty at the University of Chicago and later went to Fox Chase Cancer Center in Philadelphia.

Mintz was the first to create mouse chimeras in the early 1960s. This was a means of combining two genetically distinct mice, but rather than creating hybrids (i.e., by having the mice mate), she combined cells from each mouse in the embryonic stage, usually at the blastocyst (eight-cell) stage. So you would take four cells from one mouse zygote and four cells from another zygote and combine them, reimplant them into a mouse womb and get a normal mouse. This chimeric mouse would have features of each of the contributing mice. So it might have black fur alternating with white fur.

In 1968, Mintz undertook the following experiment. She took mice with embryos at the eight-cell stage and removed one cell from each and replaced this normal cell with a malignant cell from another mouse. This blastocyst was now re-implanted in the mouse uterus and allowed to grow to term. Mintz expected that the tumor would grow along with the mouse and there would emerge mice with tumors in them and she could study the development of tumors in utero. Instead, what she found, amazingly, was that what resulted were perfectly healthy mice, but that one-eighth of their cells were from the donated tumor. So that, for example, there were bands of black fur in an otherwise white mouse. And similarly, every organ had a mix of cells from both mice.

Apparently what had occurred was that the malignant cell had de-differentiated back to a normal multipotential stem cell. The malignant differentiation genotype had been shut off, the cells had become primitive again, and had then re-differentiated down every other cell type in the mouse to become liver, heart, brain etc. This confirmed the idea that malignant cells are simply normal cells that have differentiated in the wrong pathway. The end-result is that drugs to induce de-differentiation or further differentiation have been developed for some tumors to induce malignant cells to revert to normal—this continues to be an ongoing pharmacologic strategy.

Alfred I. Neugut, MD, PhD, is a medical oncologist and cancer epidemiologist at Columbia University Irving Medical Center/New York Presbyterian and Mailman School of Public Health in New York.

This article is for educational purposes only and is not intended to be a substitute for professional medical advice, diagnosis or treatment, and does not constitute medical or other professional advice. Always seek the advice of your qualified health provider with any questions you may have regarding a medical condition or treatment.