The Pill That Could · The Patients Who Waited

The Patients Who Waited, part 2

His CML, on every test that has been done, is undetectable. He has been off active monitoring for the deepest molecular response measures for several years now — at his age, the question of whether his MR is at 4.5 or 5.0 is no longer of great clinical interest. He still takes the drug. The drug, after a long discussion several years ago, was reduced from his original dose to a lower one, in deference to his age and his renal function. He tolerates the lower dose well. He has the side effects of being ninety-one, which are extensive. He does not, by any reasonable assessment, have the side effects of CML.

Druker spends about thirty minutes with him. The conversation is what conversations between long-known doctors and long-known patients tend to be. They talk about the man's son, who lives in Eugene. They talk about a book the man has been reading. They talk briefly, in the way that elderly patients sometimes raise such things, about how the man would like things to go when his time comes — not soon, he hopes, but not so far away anymore that the question is academic. Druker listens. He asks about pain management. He asks whether the man has talked with his son about any of this. He notes a few things in the chart.

When the man stands to leave, he steadies himself on the chair. Druker walks him to the waiting area. They shake hands. The man says ’thank you, doctor,' the way the man has said ’thank you, doctor' at the end of every appointment for almost thirty years. Druker says ’thank you for coming in.'

The next patient is already waiting.

* * *

If you sat in this clinic for a full day, the picture you would build up would not be a triumphal one. It would be quieter than that.

It would be a picture of normal medical practice, by which I mean the practice of seeing people who have a chronic condition and helping them stay well. The patients are not, by and large, dying. They are not, by and large, in crisis. They have a thing they take a pill for, and they come in to make sure the pill is still working, and the pill is, almost always, still working. Their bloods come back normal. Their bone marrows, when they get one (which is less and less often, since modern PCR-based monitoring has reduced the need for bone marrow biopsy in stable patients), are clean. Their lives are continuing in the way lives continue when they are not being interrupted by a fatal illness.

There are, on any given clinic day, exceptions to this picture. There is sometimes a newer patient who is in the early stages of treatment, working out side effects, getting used to the daily pill. There is sometimes a patient whose disease has done something unexpected — a slow rise in PCR, a question about whether the drug needs to be switched. There is sometimes a patient who has come in because they have developed something else — another cancer, another medical condition — and is here because Druker has been their oncologist for so long that he is the doctor they want to talk to. There is sometimes a patient who has not done well, whose CML has progressed, whose options through the targeted-therapy ladder have narrowed, and for whom the conversation in clinic is more like the conversations Druker had to have in 1993 — honest, careful, with limits acknowledged. These conversations have not entirely disappeared from the clinic. They are rarer.

This is what the targeted-therapy era has done in CML, in the small specific space of one disease and one clinic. The dominant feature of the practice is the absence of crisis. Patients live with their disease. They come in. They go home. They keep taking the pill. They come in again.

* * *

Some of the people from the earlier chapters of this book are no longer alive in 2026, and it is worth noting them honestly.

Janet Rowley died in 2013, at eighty-eight. She had been in the field, more or less continuously, since 1962. She had been a cytogeneticist when cytogenetics was a small and somewhat marginal subspecialty, and she had lived to see her work be the basis for the first targeted cancer therapy in history. She continued to work, in some capacity, almost until the end of her life. The Presidential Medal of Freedom that she had received in 2009 sat in her office; the Lasker Award and National Medal of Science she had received earlier had similar fates. Her colleagues, in the obituaries written after her death, used a phrase that recurred: she had been the kind of scientist who was satisfied to do the work, and to have done it, and not to have made too much fuss about it. She did not get the Nobel Prize. She probably should have. Most of the obituaries said so.

David Hungerford, who had counted the chromosomes in 1959 and 1960 — who had, with Peter Nowell, made the original observation that started this story — died in 1993 at the age of sixty-six, of a stroke. He died in the year Druker first walked into his clinic in Portland. He died several years before the phase 1 trial of the drug that would, eventually, do something with the small chromosome he had described. Peter Nowell, the other author of the 1960 paper, lived longer; he died in 2016 at the age of eighty-eight. He did get to see imatinib's approval, the IRIS data, the second-generation drugs, and a long stretch of the unfolding consequence of the original observation he and Hungerford had made. By the time of his death, the Philadelphia chromosome had been the subject of more research papers than any other chromosomal abnormality in human cancer.

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