From the Introduction to the Mariner Edition of Natural Obsessions

If I had to draw the leaves on my family tree, I would give a lot of them the jagged, angry silhouette of a cancer cell. I've lost more relatives to cancer than to anything else, and some of them at a fairly young age. My father died at 51, when a malignant melanoma tumor spread to his brain. My maternal grandfather also died at 51, of pancreatic cancer. My father's father died of colon cancer. Great aunts, great uncles, and cousins have died of cancer. So when I mull over the likeliest story line for my own death, which I do to self-indulgent to excess, I start with the assumption that it will be from cancer, and then entertain myself by wondering, when? And what kind?

Natural Obsessions is a book about the search for the molecular origins of cancer. It is a book about the nature of basic research and the blood-sweat-and bones scaffolding of two highly competitive research laboratories: Robert Weinberg's group at the Whitehead Institute of MIT, and Michael Wigler's team at Cold Spring Harbor Laboratory on Long island. It is about how scientists think, and how they feel, and how they behave. It is about the rush of ecstasy that comes when an experiment works, the virulent paralysis that follows failure, and the many stretches of confusion and ambiguity in between. It is about how scientists are as human as the rest of us, only smarter and with less attractive foot wear.

What the book most emphatically is not about is the search for a cure for cancer. As I explain in the first chapter, most basic scientists do not search for cures. They ask how the cell grows or stops growing. They asked about dominant cancer genes and tumor-suppressor genes, signaling pathways and membrane ruffling. They don't like anybody mentioning the phrase " cure for cancer." It makes them nervous. Are taxpayers getting impatient? They worry. Will the government cut off our grant money and make us look for real jobs?

Basic researchers don't like talking about cures for cancer, and neither, I admit, do I. I am scared of cancer, and I fret hypochondriacally about every headache or new freckle. I would love to imagine that the people whom I profile in natural obsessions, or any of the thousands of others in the field of oncogene, or cancer gene, research, will soon make spectacular breakthroughs with immediate bedside applications. I would love to imagine that scientists are on the verge of conquering cancer, yet I can't say I'm confident that they are. They may be, or they may not be. Nobody knows. In the 11 years since this book first appeared, scientists have made relatively little progress in applying the fruits of basic research to the treatment of cancer. They have not come up with any magic bullets; they haven't even found the right gun yet. It makes sense to hope that a firm understanding of the genes and proteins responsible for cancerous transformation will yield more effective therapies. Right now, oncologists rely on the standard treatment troika that they have relied on for decades: surgery, radiation, and chemotherapy--or, as the blunt tongues among them describe it, burn, slash, and poison. Chemotherapy and radiation are quite good at killing cancer cells, but they are also notoriously good at killing normally dividing cells, which is why the therapies lead to side effects such as intense nausea, hair loss, and immune suppression, and why the treatments cannot always be used in doses high enough to destroy every last tumor cell. If researchers could design drugs that target mutant genes or abnormal proteins found only in malignant cells, they theoretically could destroy those cells while leaving normal tissue unharmed.

Researchers have identified a large number of genetic mutations that are specific to cancer cells. one of them affects the so-called ras gene, a major molecular figure in this book and a subject of ongoing research among scientists, pharmaceutical companies, and biotechnology firms. The normal ras gene operates in the body to help orchestrate a healthy cell division. But when the gene in one cell mutates, it can help instigate the growth of a malignancy. The mutant ras gene is a nasty character, found in about 25% of all human tumors. It would be magnificent to have a drug that homes in on the mutant ras gene, or on the aberrant protein that the mutant ras gene specifies. Researchers have worked mightily to develop drugs against ras. So far, they don't have one. For all the hype surrounding the biotechnology business, and despite the inherent logic behind the targeted approach to cancer therapy, designing drugs is extremely difficult. Even drugs that initially look selective often end up with a suite of unexpected side effects, and any drug that is going to be powerful enough to destroy or disable a full-blown cancer, when millions of malignant cells are disseminated throughout the body, is likely to have a few harrowing surprises up its side chains.

Progress in this area is always a matter of one step forward, one slap in the face. In Chapter 9, I describe the Weinberg lab's work on an oncogene called neu, which has since been given a double name, Her-2/neu. Recently, Dennis Slamon, of the university of California at Los Angeles, designed a drug called herceptin, a monoclonal antibody that interferes with the Her-2/neu gene in tumor cells. Slamon has fought, heroically and monomaniacally, to develop the drug and bring it to clinical trials, and early results suggest that it shows promise for the treatment of advanced breast cancer, when the Her-2/neu gene often is hideously hyperactive and has amplified in numbers to grotesque proportions. But herceptin cannot be called a cure; in some cases it can prevent recurrence or lead to remission, but in others its use appears to increase the risk that stray breast cancer cells will spread to the brain, beyond any therapy's reach....

So I don't like talking about cures. As far as I can tell, the assessment of Michael Bishop, of the university of California at san Francisco, which I quote in Chapter 1, is still correct. "There's been far too much hype in this business, too much cocksureness," he said. "Anybody who walks around and says that we've got this problem almost licked is a fool, a knave, or both."

Yet if we configure what we view as "the problem" and ask not "When are we going to cure cancer?" but instead "What have we learned by studying cancer?" then the answer has to be: an extraordinary amount. It is the second question rather than the first with which my book ultimately is concerned. Through studying the cancer cell, that fluttering little leaf of death, we paradoxically have learned about the roots of life. The cancer cell is the distilled cell, doing what all cells are designed to do, which is proliferate; and because the cancer cell does its job so tirelessly and ostentatiously, it can be analyzed. In dissecting the cancer cell, we get a handle on the healthy cell, its organization, rhythm, and aesthetics, and what it takes to live and to perpetuate life. We have learned much, and we are learning more by the day — or by the night, when many scientists do their best work. This is a spectacular enterprise, this exploration into the rudiments of the cell. It deserves our applause, our communal pride, and our tax dollars. If we were given our oversized frontal lobe to understand nature and the universe, then we have a duty, a moral imperative, to study the cell, to scratch away at its pitiless complexity until it squeals. We are obliged to keep exploiting the cancer cell, even as we have trouble taming it.

And we're lucky that biologists love to do this sort of work, because it is grueling, often tedious, badly paid, and anonymous. It is practically impossible to become a scientific celebrity. Look at poor Harold Varmus, who appears in this book and who has subsequently won a Nobel Prize with Michael Bishop for their work on oncogenes. He went on to become the director of the National Institutes of Health, one of the most prominent scientific posts imaginable. No matter. On hearing that Varmus would be giving the commencement address at Harvard University in 1996, the editors of the student newspaper, the Harvard Crimson, expressed their indignation. "Dr. Who?" was the title of their editorial. Sure, the guy may have won a Nobel Prize, and he may be the head of the biggest research organization on the planet, but who the hell is he? Couldn't the university officials have invited someone more "glamorous"? the paper asked. Undeterred by the rudeness of the Harvard brats, Varmus gave the address. He is, after all, accustomed to rudeness. Scientists are trained to question every bit of data they see and to speak their mind, however roughly. Such skills can spill over into their social interactions, as in, "You've gained weight, haven't you?" or "Did you know you have a pimple on your face?"

Scientists are not high-minded martyrs, not by a long shot of any heigh-ho silver bullet. They may rarely gain widespread public fame, but their egos are large and in need of chronic stoking, which they seek from their peers. Scientists compete fiercely for professional acclaim; they want to be known and respected by those who know better, who understand what they do. They want to follow their whims and instincts, they want to solve puzzles, and they want to learn how things work....They love science with their heads the way most of us love people with our hearts. They love it at 3:43 in the morning, they love it on Sabbaths and holidays, they love it when they should be so bored they're starting to drool. Their latest results may look like the smears on a preschooler's placemat, but still they scan the results for a scrap of sense and get excited and want to do more science. In the many years I've been writing about science, I've had my gripes about its practitioners. Science is like Paris, I've thought irritably: it would be a great place if it weren't for the Parisians. Yet always I have admired and envied scientists for the depth with which they love their calling. In this book, I try to give a sense of that love. The names and technical details of the science may change, but the love, at least, keeps on burning.