The Pill That Could

Chapter 2: The Translocation

In a small office at the University of Chicago, in the spring of 1973, Janet Rowley is laying out photographs of chromosomes on her desk.

There are forty-six in each photograph. She has cut each one out of a printed micrograph of a single dividing cell, taken from a patient with leukemia, stained with a chemical that makes parts of each chromosome fluoresce under ultraviolet light. The photographs are small and grainy. Each shows a single chromosome, photographed end-on, looking like a pale rod with bands of darker and lighter stripes running across its length.

She is matching them up. The work is patient and slow and looks, from the outside, exactly like solitaire. From the inside it is something else.

The work travels with her. Some of the time she is at her office desk. Some of the time she is at home, on the dining room table, cutouts spread across the polished wood, her four sons either grown or out of the house, her husband — a pathologist at the same university — long used to seeing the chromosomes laid out alongside his evening reading. She has been doing this kind of work, on and off, for most of a decade. She still works part-time. She still has, formally, the part-time appointment she took when her children were small.

The chromosomes she is looking at this spring come from patients with chronic myeloid leukemia. She is looking, specifically, for the Philadelphia chromosome — the small chromosome 22 that Nowell and Hungerford reported thirteen years earlier. She has found it, in patient after patient, and confirmed what is already known: the Philadelphia chromosome is real, and it shows up reliably in CML.

What she has been seeing more recently, though — with a new staining technique she learned during a sabbatical in England — is that the Philadelphia chromosome is not alone in being abnormal.

Chromosome 9, in these same cells, has something extra on it.

* * *

Janet Rowley grew up in Chicago, the only child of a librarian mother and a college-instructor father. She finished high school early, started the University of Chicago's accelerated program at fifteen, and finished medical school at twenty-three. She married Donald Rowley, a fellow medical student who would become a pathologist, the day after she got her degree. They had four sons in the next ten years.

Through those ten years, and for some years after, Rowley worked at her medical career in the way it was widely assumed a woman with four children would work at one if she did at all — part-time, fitting it around the home life, in clinics and labs that would have her on those terms. She did not stop working. She also did not become a full-time researcher, in the way a man with the same training would have, until much later in her career.

This is worth noticing, because the science she is doing in 1973 is the kind of slow, careful, attention-intensive work that benefits from a researcher who has spent fifteen years patiently looking at things rather than rushing toward results. Whether or not she would have done it differently in a less constrained career, the career she had was one in which she had learned, very thoroughly, how to see chromosomes.

She had moved into the chromosome work properly in 1962, joining a group at the University of Chicago that was studying cells from patients with developmental abnormalities. By the late 1960s she was a serious cytogeneticist. In 1970 she took her family to England for a sabbatical year — a rarity for a part-time appointment, and a piece of her career she had to push for — and worked in Oxford in the lab of a researcher named Henry Harris. While she was there, the field she worked in changed.

* * *

What changed was that someone figured out how to see inside a chromosome.

Up until 1970, a stained chromosome looked like a uniform bar — a pale rod, with the centromere somewhere along its length, and not much else to distinguish it. To tell one chromosome from another you measured length and centromere position and grouped them into a few broad categories, and that was about it. You could spot major abnormalities — the Philadelphia chromosome was unmistakably small — but anything subtle, anything where two chromosomes might look similar but be different in ways that mattered, was effectively invisible.

Then a Swedish biophysicist named Torbjörn Caspersson, working with a team in Stockholm, tried something unusual. He stained chromosomes with a chemical called quinacrine mustard, which is a derivative of an old antimalarial drug, and which has the property of binding preferentially to certain regions of DNA. Specifically, it binds to regions rich in the bases adenine and thymine — two of the four molecular letters of DNA — and ignores regions that are richer in the other two, guanine and cytosine. Then he illuminated the stained chromosomes with ultraviolet light. The quinacrine fluoresced. The AT-rich regions lit up. The GC-rich regions stayed dark.

What appeared, when he looked through the microscope, was a striped pattern. Each chromosome had a sequence of bright and dark bands along its length, like a barcode. And the pattern was reproducible. The bands on a particular chromosome appeared in the same order, with the same spacing, in cell after cell, in person after person. Each of the twenty-three human chromosomes had its own distinctive pattern. You could now tell them apart not just by size but by their internal structure.

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