p53 Takes Center Stage

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When Drs. Michael Bishop and Harold Varmus started their work together the two scientists were somewhat out on a limb, for in 1970 many of their peers were skeptical of the theory that cancer is a disease of the genes, since there was no direct evidence for it.

—Sue Armstrong

Title: p53: The Gene That Cracked the Cancer Code
Author: Sue Armstrong
Publisher: Bloomsbury Publishing
Publication date: November 20, 2014
Price: $19.98; hardcover, 288 pages


Completed in April 2003, the Human Genome Project was one of the greatest feats of scientific exploration, an inward voyage of discovery to sequence and map all of the genes of our species. Our genome contains an estimated 20,000 to 25,000 human protein coding genes, and each gene, in its own informational way, tells a story about the dizzying complexities of life.

From a rose petal to a blue whale, all life on earth shares a commonality: DNA. Life’s unique building block began its publicity tour on February 28, 1953, when Francis Crick and James Watson interrupted the lunch-time crowd at a Cambridge, England, watering hole called The Eagle, announcing that they had “discovered the secret of life” after they had come up with their proposal for the structure of DNA. Several decades later, other researchers would discover that the secret of life was, in many ways, the secret of cancer.

With so many genes to choose from, those who wish to write about them must pick out the true stars of our genome, such as The Philadelphia Chromosome: A Genetic Mystery, a Lethal Cancer, and the Improbable Invention of a Lifesaving Treatment, by Jessica Wapner (reviewed in the September 15, 2013, issue of The ASCO Post). Ms. Wapner took a gene very well known to the readers of this journal and gave a meticulous frame-by-frame inspection of its history and the renowned and less-renowned scientists and doctors who played a role in the Philadelphia chromosome’s discovery and ultimate development of a successful drug for leukemia. It was a good book because Ms. Wapner carefully wove together the basic and applied science within the stories of the dedicated researchers as they maneuvered the process of bringing pharmaceuticals to market.

Putting the Puzzle Pieces Together

Science writer Sue Armstrong tackles the story of another famous gene in her new book p53: The Gene That Cracked the Cancer Code, a highly informative narrative about the quest for scientific understanding and the promise that recent advances in molecularly targeted pathways hold for the oncology community. She begins by giving the reader a nuts and bolts description of cancer biology, nothing new here for the readers of The ASCO Post.

In Chapter 2, Ms. Armstrong lays the book’s foundation, telling the compelling story of how Drs. Michael Bishop and Harold Varmus were putting the pieces of an exquisite puzzle together: describing the cause of cancer. For oncology fellows rushing about in clinics from Memorial Sloan Kettering to Dana-Farber, this line in the book should serve as a stark reminder of how far we’ve come in just a few decades, thanks to the giants on whose shoulders they now stand.

The author writes, “When Drs. Michael Bishop and Harold Varmus started their work together the two scientists were somewhat out on a limb, for in 1970 many of their peers in the scientific community were skeptical, even frankly disbelieving, of the theory that cancer is a disease of the genes, since there was no direct evidence for it.”

A Host of Personalities

From there, Ms. Armstrong races headlong into the scientific process that led several groups of scientists, most notably one led by Professor Sir David Lane, to the discovery of the p53 protein. It is an interesting section because the esteemed scientists were barking up the wrong genetic tree, thinking that p53 was an oncogene. In telling of the quest to identify the “real p53” and what it means to the carcinogenic process, the reader gets treated to a deep understanding of the complexities in laboratory research, the somewhat mysterious place where the startling advances in cancer discovery begin.

Not surprisingly, Ms. Armstrong has a host of big personalities to sort out, and at times it’s difficult to keep them and their particular contributions to the p53 story in order. Readers of The ASCO Post will enjoy when she finally arrives at the office of one of those big personalities, Bert Vogelstein, who along with his students discovered that p53 not only played a role in tumorigenesis, but it was a common denominator of human tumors, mutated in the majority of them.

Wisely, the author uses mini biographies and amusing anecdotes to break up the dry scientific narrative. “On a stunningly hot afternoon in July 2012, I travelled to Baltimore to meet Dr. Vogelstein, climbing the stairs overlooking the original old hospital of Johns Hopkins…. His lab is famed almost as much for its fun as its hard work. For years, Dr. Vogelstein headed a rock band, a bunch of musicians from his lab who called themselves Wild Type and played at scientific venues. The band broke up when the drummer’s wife died of leukemia, and he dropped out to take care of the kids.” That’s good stuff, and Ms. Armstrong is skilled enough to spice the narrative with human portraits without ever feeling like its filler.

Heavy on the Science

Ms. Armstrong’s book is informative and entertaining for those with a medical or scientific background or for readers who have a dedicated interest in scientific breakthroughs, but it may be less appealing for more general readers. For example, in the chapter The Smoking Gun, she illustrates the intriguing role of p53 in the effort to link smoking to lung cancer. This was an epic battle in the history of cancer, pitting courageous doctors against Big Tobacco, and the victory has saved countless millions of lives.

While describing this legendary struggle against the tobacco industry, the author writes, “Crucially, while codons 248 and 273 are mutation hot spots in many types of cancer, the database revealed that codon 157 is found exclusively in lung tumors…. The fingerprint of BPDE was all over the p53 database.” Here, as in other sections, Ms. Armstrong’s dedication to getting the science right, proves too jargon-laden and bogs the pace down to a crawl.

Make no mistake: This is an important subject, one that oncology fellows should read about, because it will inform them about the processes that propelled oncology forward. Moreover, the field needs a constant supply of fiercely curious minds such as those who discovered p53 and learned how to use it as a tool in the fight against cancer.

Unfortunately, the dramatic punch and inspirational messaging of this highly informative book often get lost in acronyms and dry scientific explanations, which could have been streamlined for a better read. Ms. Armstrong is an accomplished science writer, and perhaps writing a book about p53 was a good idea, but sometimes a good idea for a book is a better idea for a magazine article. Such is the case with p53: The Gene That Cracked the Cancer Code.