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Bar Coding and Cancer Research

The New York Times

N0vember 29, 2021

Gina Kolata

Stamping Bar Codes on Cells to Solve Medical Mysteries

By tracking every cell in an organism, scientists are working out why certain cancer treatments fail, which could lead to improved medicine.

No one really knew why some patients with a white blood cell cancer called chronic lymphocytic leukemia, or C.L.L., relapsed after treatment and got a second cancer. Were some cancer cells just resistant?

An unexpected answer to this mystery has been found using a new technique that researchers call bar coding: The treatment does not always target the right cells.

Scientists discovered that the cancer does not always originate in the mature bone marrow cells where it is found and where textbooks say it originates. Instead, for some patients, the mother lode of the cancer can be primitive bone marrow cells, the stem cells, that give rise to all of the body’s white and red blood cells. Those cells, not affected by the chemotherapy treatment, can spawn new cancer cells, causing a relapse.

The discovery is one early fruit of the bar coding method, which is aiding the study of the origins of cancer and other diseases. The results are too new to have led to patient therapies. But they are leading to provocative discoveries that are expected to inspire novel methods for treating diseases.

The method works by marking individual cells with a stamp that is passed on to all of a cell’s progeny. Researchers can look at a cell, note its bar code and trace its lineage back to its parents, grandparents, great-grandparents — all the way back to its origins — because each cell that arose from the original bar coded cell has the same stamp.

The idea for bar coding during embryonic development originated with Dr. Jay Shendure and his colleagues at the University of Washington, and this class of methods was anointed the breakthrough of the year by Science magazine in 2018. Now there is a variety of methods for bar coding ranging from embryo cells to cancer cells to mature cells.

For example, Dr. Shendure and another group of colleagues at the University of Pennsylvania are using bar codes in mice with pancreatic cancer to study the spread of cancer cells in their bodies.

In the case of C.L.L. above, Dr. Vijay Sankaran at Boston Children’s Hospital and his colleagues bar coded human cancer cells by taking advantage of innocuous, naturally occurring mutations that mark individual cells and are inherited by their progeny. Bar coding, Dr. Sankaran said, “starts to give us a view of cancer that we never had before.”

The technique also revealed a surprising result to Dr. Leonard Zon of Harvard Medical School. He wanted to study clonal hematopoiesis of indeterminate potential, or CHIP, a common but poorly understood condition that is common in older people and increases the risk for cancer and heart disease. CHIP occurs when the progeny of a single blood stem cell take over all or a large part of the bone marrow, squeezing out other stem cells.