Januvia Lawyer: Cancer wreaks havoc in almost every part of the human body. Tumors strike the brain and the gut, muscles and bones. Some grow slowly; others are more aggressive and expand quickly. Their presence in human tissues signals chaos and a break­down of normal function. Cancer brings unwelcome change to a biological machine that is perfect, marvelously beautiful, and complex beyond measure. Wherever tumors appear, they take on the appearance of alien life forms, invaders that enter the body through stealth and begin their programs of destruction from within. But appearances deceive: The truth is much more subtle and endlessly interesting.

Tumors are not foreign invaders. They arise from the same material used by the body to construct its own tissues. Tumors use the same components—human cells-—to form the jumbled masses that disrupt biological order and func­tion and, if left unchecked, to bring the whole complex, life- sustaining edifice that is the human body crashing down. How are human tissues put together from single cells? The description above might suggest the involvement of master builders who oversee crews of workers, directing them in the detailed construction of normal and malignant tissues. In reality, there are no overseers forcing throngs of cells to line up and assemble themselves into normal or can­cerous tissues. Architectural complexity in living tissue comes from the bricks themselves, the individual cells. Con­trol is exercised from the bottom up.

Normal and malignant cells know how to build. Each car­ries its own agenda that tells it when it should grow and di­vide and how it should aggregate with other cells to create organs and tissues. Our bodies are nothing more than highly complex societies of rather autonomous cells, each retaining many of the attributes of a fully independent organism. Right there, we confront great beauty and profound danger. The beauty lies in the coordinated behavior of so many cells to create the single, highly functional cooperative that is the hu­man body. The danger lies in the absence of a single oversee­ing master builder, which seems to put the whole enterprise at great risk. Granting autonomy to trillions of worker cells in­vites chaos. When, as usually happens, these cells are well be­haved and public-spirited, extraordinarily complex order ensues. But on occasion, a cell may choose to go its own way and invent its own novel version of a tissue or organ. It is then that we see the much-feared chaos that we call cancer.

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Januvia Lawyer: Most human tumors comprise a billion or more cells be­fore we become aware of them. The cells within a tumor dif­fer from their normal counterparts in many respects, exhibiting distinctive shapes, growth properties, and metab­olism. The sudden appearance of such a horde of cells would seem to reflect some recent mass conversion, in which millions of normal cells enlisted overnight in the ranks of a tumor mass. Once again, appearances deceive. The creation of a tumor is an extraordinarily slow process, often extending over decades. The cells forming a tumor are all lineal descendants of a single progenitor, a distant ancestor that lived many years before the tumor mass became apparent. This founder, this renegade cell, decided to go off on its own, to begin its own growth, program within one of the body’s tissues. There­after, its proliferation was controlled by its own internal agenda rather than the needs of the community of cells around it.

So there were no millions of recruits, only a single one that spawned a vast horde of like-minded descendants. The billions of cells in a tumor are cast in the image of their rene­gade ancestor. They have no interest in the well-being of the tissue and organism around them. Like the founder cell, they have only one program in mind: more growth, more replicas of themselves, unlimited expansion. The chaos they create makes it clear how very dangerous it is to entrust each cell in the human body with its own measure of independence. Still, that is how we are put to­gether, and how all complex, many-celled organisms have been designed for the past 600 million years. Learning this, we realize that the chaos of cancer is not a modern affliction but a risk run by all multicellular organisms, from ancient to modern. Indeed, given the trillions of cells in the human body, is it not a wonder that cancer does not erupt often dur­ing our long lives?

The notion that cancer was not a random, spontaneous de­generation of the body’s tissues, but instead was actively in­duced, radically changed the thinking of many cancer researchers. If external agents triggered die disease, perhaps they could be identified and their mechanisms of action studied. Perhaps the entire process from the initial en­counter with a cancer-causing agent to the appearance of a cancer could be uncovered. So, toward the end of the nine­teenth century, scientists throughout the world tried to recre­ate cancer in laboratory animals—mice, rats, and rabbits. For years, all such attempts failed.

The first successes came in Japan in the first decade of die new century. Katsusaburo Yamagiwa took instruction from the far earlier studies of European chimney siveeps. Percival Pott’s initial observations of high rates of scrotal cancer in London chimney sweeps had been followed several decades later by the work of others who found that chimney sweeps on the Continent had much lower rates of this tumor. The difference seemed to be related to personal hygiene practices. The British chimney sweeps, like many of their eighteenth-century coun­trymen, rarely took baths, while the chimney sweeps on the Continent bathed frequendy. It seemed that creosote tars from the London flues stuck to the skin of die British sweeps and triggered cancer unless washed away quickly.

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