Carcinogenesis

Environmental & Science Education, STEM, Health, Medicine, Science & Society, Nature of Science, History of Science

Ed Hessler

This entry is a nudge. I recommend an essay by Siddhartha Mukerjee titled "Sleeper Cells," (The New Yorker, December 18, 2023). It is about those elusive carcinogens and catching more of them.

Mukerjee is the author of The  Emperor of All Maladies:  A Biography of Cancer for which he received a 2011 Pulitzer Prize. In that book his humanity shines as if it were a super nova. I could easily recommend The New Yorker essay for its writing alone but I've a larger hope - that you might be interested in recent developments in cancer research. It also is an essay on how biomedical science works, its nature and history

I pitched most of what I'd written in favor of describing the essay's general topography. I felt as though I was turning gold into lead. I may have still done that. The divisions are arbitrary. The sections are not that discrete.

-- Prologue

It is about the so-called Ames test. "the standard lab technique for screen substances that may cause cancer." It was never a comprehensive tool which Ames and others knew from the beginning. Mukerjee reviews some of the mysteries of carcinogenesis. I think you will enjoy the story of how Bruce Ames happened to develop the test. It was somewhat serendipitous.Upon reading the ingredients in a package of what we think of as junk food he wondered about their safety.. Mukerjee introduces us to research results that "didn't fit the standard model of carcinogenesis." This led to a question about the role of inflammation: "What kind of substance irritates its victims to death?"  In other words this is a question about mechanisms of carcinogenesis.

-- Main body of the Essay

 Mukerjee uses two Arthur Conan Doyle stories, "The Adventure of the Speckled Band" and "The Hound of the Baskervilles." Each expands the mystery just as "chemical irritants presented carcinogen hunters with a structurally similar problem," that is, they "work only in combination with other chemicals." This calls for a more complex test. An MD, Irving Selikoff whose practice was in Paterson, NJ and who began treating Union Asbestos and Rubber Company workers. Selikoff was current with medical literature and a keen observer. He documented the incidence of lung, stomach, colon, and rectal cancer in asbestos workers. All were considerably "higher than expected." The "how" though remained elusive.

"In science," Mukerjee observes, "a clamorous consensus often begins as a whisper." He follows that whisper through "cancerous scrotal sores" in London's chimney sweeps. The trail is not obvious. "[I]n almost one in ten cases, we can't identify a clear mechanism for the development of lung cancer even in smokers gives all the more reason to think that we may be missing a plenitude of cancer-causing agents." Nature is very good at hiding things from us. Not designed, of course, merely a feature of the natural world

Mukerjee returns to a researcher he mentions early in the essay which leads to a question, something to wonder about. "Could there be a universe of promoters that we'd been missing because we hadn't been looking in the right place?"  The researcher points him to Charles Swanton, evidence of the collegiality of science and how larger puzzles are solved by workers on different facets of the problem. This story becomes even more complex and interesting. Is cancer, as Swanton suggests, a disease of clonal competition? It looks like "mutant clones are already there, sleeper cells awaiting activation. ...With carcinogenesis, as with so much in life, the right combination of nature and nurture is required."

Swanton likely reminded Mukerjee that Ames and his colleagues mentioned another cancer correlate---proximity to major roadways, gasworks, industrial plants, and coal fires, and thus by extension, exposure to high levels of air pollution." Mukerjee summarizes a study from Swanton's lab on this cancer correlate, published in Nature in early 2023 "which ends on an ominous note: 'Our data suggest a mechanistic and causative link between air pollutants and lung cancer, as previously proposed, and substantiate earlier findings on tumour promotion, providing a public health mandate to restrict particulate emissions in urban areas.'"

The Ending of the Essay

Mukerjee ends by describing some possibilities for carcinogens that work by changing the environment of the cancer cells. His lab "works on similar" clusters. He includes an important comment on science using literature as the framework. Mukerjee had been told by a friend that "'The one way to identify a great work of literature, is that the person who begins the novel and the person who finishes it are never going to be the same. The novel changes you.'" Mukerjee observes that "The same might be true for great work in science. It fundamentally changes the way you see the world."

This sheds a beacon of light on the impressive achievement of the Swanton Lab. The team "had wrestled the mystery down using epidemiology, toxicology, immunology, and human genetics, and then pulled them together into a causal, biological plausible mechanism for carcinogenesis."

Before leaving London, Mukerjee revisited the world of Sir Arthur Conan Doyle "in the spirit of completing the journey," and took a cab to 221B Baker Street.

 

P.S. As I expected and hoped there was a letter published about Mukerjee's essay (The New Yorker, January 15, 2024) from an M.D. He calls attention to a paper published in 1943 which he describes as "a beautiful experiment, by Salvador Luria and Max Delbruck, that provided clean data supporting the idea of preexisting mutations. ... The virus merely "selected" for resistant bacteria". The writer wondered "with the powerful DNA-sequencing methods available today (whether) a similar experiment (using) mammalian cells to reveal latent vulnerabilities." The writer also calls our attention to a Nobel Prize in Physiology or Medicine (1969) these two towering figures shared (also Alfred Hershey, another tree) "for their contributions to genetics." 

Oh, how I wish responses from the author was standard.