Siddhartha Mukherjee


American Physician, Biological Scientist and Author, Awarded Pulitzer Prize for his book, The Emperor Of All Maladies: A Biography of Cancer

Author Quotes

It is not what you have, as a certain Brazilian samba instructor once told me, it is what you do with it.

Like so many doctors, Rieff recalls, he spoke to us as if we were children but without the care that a sensible adult takes in choosing what words to use with a child. The sheer inflexibility of that approach

My book is an attempt to answer her question by going back to the origin of the disease and showing its development through history. I called it a biography of cancer, because it draws a portrait of an illness over time.

Other cancer-causing viruses, such as SV40 and human papillomavirus (HPV), would eventually be discovered in 1960 and 1983, respectively.

Science embodies the human desire to understand nature; technology couples that desire with the ambition to control nature. These are related impulses?one might seek to understand nature in order to control it?but the drive to intervene is unique to technology. Medicine, then, is fundamentally a technological art; at its core lies a desire to improve human lives by intervening on life itself. Conceptually, the battle against cancer pushes the idea of technology to its far edge, for the object being intervened upon is our genome. It is unclear whether an intervention that discriminates between malignant and normal growth is even possible. Perhaps cancer, the scrappy, fecund, invasive, adaptable twin to our own scrappy, fecund, invasive, adaptable cells and genes, is impossible to disconnect from our bodies. Perhaps cancer defines the inherent outer limit of our survival. As our cells divide and our bodies age, and as mutants accumulate inexorably upon mutations, cancer might well be the final terminus in our development as organisms. But our goals could be more modest. Above the door to Richard Peto?s office in Oxford hangs one of Doll?s favorite aphorisms: Death in old age is inevitable, but death before old age is not. Doll?s idea represents a far more reasonable proximal goal to define success in the war on cancer. It is possible that we are fatally conjoined to this ancient illness, forced to play its cat-and-mouse game for the foreseeable future of our species. But if cancer deaths can be prevented before old age, if the terrifying game of treatment, resistance, recurrence and more treatment can be stretched out longer and longer, then it will transform the way we imagine this ancient illness. Given what we know about cancer, even this modest goal would represent a technological victory unlike any other in our history. It will be a victory over our own inevitability?a victory over our genomes.

Technological innovations do not define a science; they merely prove that medicine is scientific.

The evolution of Rous sarcoma virus, then, was purely an accident. Retroviruses, Temin had shown, shuttle constantly out of the cell?s genome: RNA to DNA to RNA. During this cycling, they can pick up pieces of the cell?s genes and carry them, like barnacles, from one cell to another. Rous sarcoma virus had likely picked up an activated src gene from a cancer cell and carried it around, creating more cancer. The virus was no more than an accidental courier for a cancer-causing gene that had originated in a cancer cell?a parasite parasitized by cancer.

The philosopher of science Karl Popper coined the term ?risky prediction? to describe the process by which scientists verify untested theories. Good theories, Popper proposed, generate risky predictions. They presage a unanticipated fact or event that runs a real risk of not occurring or being proven incorrect. When this unanticipated fact proves true or the event does occur, the theory gains credibility and robustness. Newton?s understanding of gravitation was most spectacularly validated when it accurately presaged the return of Halley?s comet in 1758. Einstein?s theory of relativity was vindicated in 1919 by the demonstration that light from distant stars is ?bent? by the mass of the sun, just as predicted by the theory?s equations.

There is a very moving and ancient connection between cancer and depression.

Today when I see a patient with CML, I tell them that the disease is an indolent leukemia with an excellent prognosis, that they will usually live their functional life span provided they take an oral medicine, Gleevec, for the rest of their lives.

Yet the hunger to treat patients still drove Farber. And sitting in his basement laboratory in the summer of 1947, Farber had a single inspired idea: he chose, among all cancers, to focus his attention on one of its oddest and most hopeless variants?childhood leukemia. To understand cancer as a whole, he reasoned, you needed to start at the bottom of its complexity, in its basement. And despite its many idiosyncrasies, leukemia possessed a singularly attractive feature: it could be measured. Science begins with counting. To understand a phenomenon, a scientist must first describe it; to describe it objectively, he must first measure it. If cancer medicine was to be transformed into a rigorous science, then cancer would need to be counted somehow?measured in some reliable, reproducible way. In this, leukemia was different from nearly every other type of cancer. In a world before CT scans and MRIs, quantifying the change in size of an internal solid tumor in the lung or the breast was virtually impossible without surgery: you could not measure what you could not see. But leukemia, floating freely in the blood, could be measured as easily as blood cells?by drawing a sample of blood or bone marrow and looking at it under a microscope. If leukemia could be counted, Farber reasoned, then any intervention?a chemical sent circulating through the blood, say?could be evaluated for its potency in living patients. He could watch cells grow or die in the blood and use that to measure the success or failure of a drug. He could perform an experiment on cancer.

An Irish surgeon, Denis Burkitt, discovered an aggressive form of lymphoma?now called Burkitt?s lymphoma?

But the heritability of a trait, no matter how strong, may be the result of multiple genes, each exerting a relatively minor effect. If that was the case, identical twins would show strong correlations in g, but parents and children would be far less concordant. IQ followed this pattern. The correlation between parents and children living together, for instance, fell to 0.42. With parents and children living apart, the correlation collapsed to 0.22. Whatever the IQ test was measuring, it was a heritable factor, but one also influenced by many genes and possibly strongly modified by environment ? part nature and part nurture.

Cancer at the fin de siecle, as the oncologist Harold Burstein describes it, resides at the interface between society and science. It poses not one but two challenges. The first, the biological challenge of cancer, involves harnessing the fantastic rise in scientific knowledge?to conquer this ancient and terrible illness. But the second, the social challenge, is just as acute: it involves forcing ourselves to confront our customs, rituals, and behaviors. These, unfortunately, are not customs or behaviors that lie at the peripheries of our society or selves, but ones that lie at their definitional cores: what we eat and drink, what we produce and excrete into our environments, when we choose to reproduce, and how we age.

Cancer, then, is quite literally trying to emulate a regenerating organ?or perhaps, more disturbingly, the regenerating organism. Its quest for immortality mirrors our own quest, a quest buried in our embryos and in the renewal of our organs. Someday, if a cancer succeeds, it will produce a far more perfect being than its host?imbued with both immortality and the drive to proliferate. One might argue that the leukemia cells growing in my laboratory derived from the woman who died three decades earlier have already achieved this form of perfection.

Even an ancient monster needs a name. To name an illness is to describe a certain condition of suffering?a literary act before it becomes a medical one. A patient, long before he becomes the subject of medical scrutiny, is, at first, simply a storyteller, a narrator of suffering?a traveler who has visited the kingdom of the ill. To relieve an illness, one must begin, then, by unburdening its story. The

Halsted called this procedure the radical mastectomy, using the word radical in the original Latin sense to mean root; he was uprooting cancer from its very source.

I came here to get treatment, not consolations about hospice, she finally said, glowering with fury.

In 1838, Matthias Schleiden, a botanist, and Theodor Schwann, a physiologist, both working in Germany, had claimed that all living organisms were built out of fundamental building blocks called cells. Borrowing and extending this idea, Virchow set out to create a cellular theory of human biology, basing it on two fundamental tenets. First, that human bodies (like the bodies of all animals and plants) were made up of cells. Second, that cells only arose from other cells?omnis cellula e cellula, as he put it. The two tenets might have seemed simplistic, but they allowed Virchow to propose a crucially important hypothesis about the nature of human growth. If cells only arose from other cells, then growth could occur in only two ways: either by increasing cell numbers or by increasing cell size. Virchow called these two modes hyperplasia, and hypertrophy. In hypertrophy, the number of cells did not change; instead, each individual cell merely grew in size?like a balloon being blown up. Hyperplasia, in contrast, was growth by virtue of cells increasing in number. Every growing human tissue could be described in terms of hypertrophy and hyperplasia. In adult animals, fat and muscle usually grow by hypertrophy. In contrast, the liver, blood, the gut, and the skin all grow through hyperplasia?cells becoming cells becoming more cells, omnis cellula e cellula e cellula.

In BRCA-1 has a 50 to 80 percent chance of developing breast cancer in her lifetime (the gene also increases the risk for ovarian cancer), about three to five times the normal risk.

In the late 1920s, a decade after Taft?s proposal had been tabled, cancer research found a new and unexpected champion?Matthew Neely, a dogged and ebullient former lawyer from Fairmont, West Virginia, serving his first term in the Senate. Although Neely had relatively little experience in the politics of science, he had noted the marked increase in cancer mortality in the previous decade?from 70,000 men and women in 1911 to 115,000 in 1927. Neely asked Congress to advertise a reward of $5 million for any information leading to the arrest of human cancer.

It is one thing to try to understand how genes influence human identity or sexuality or temperament. It is quite another thing to imagine altering identity or sexuality or behavior by altering genes.

Like the English novel, or the face, say, the human genome can be lumped or split in a million different ways. But whether to split or lump, to categorize or synthesize, is a choice. When a distinct, heritable biological feature, such as a genetic illness (e.g., sickle-cell anemia), is the ascendant concern, then examining the genome to identify the locus of that feature makes absolute sense. The narrower the definition of the heritable feature or the trait, the more likely we will find a genetic locus for that trait, and the more likely that the trait will segregate within some human subpopulation (Ashkenazi Jews in the case of Tay-Sachs disease, or Afro-Caribbeans for sickle-cell anemia). There?s a reason that marathon running, for instance, is becoming a genetic sport: runners from Kenya and Ethiopia, a narrow eastern wedge of one continent, dominate the race not just because of talent and training, but also because the marathon is a narrowly defined test for a certain form of extreme fortitude. Genes that enable this fortitude (e.g., particular combinations of gene variants that produce distinct forms of anatomy, physiology, and metabolism) will be naturally selected.

Nature is not a temple but a ruin. A beautiful ruin, but a ruin all the same.

Our ability to read out this sequence of our own genome has the makings of a philosophical paradox. Can an intelligent being comprehend the instructions to make itself? ?John Sulston Scholars

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American Physician, Biological Scientist and Author, Awarded Pulitzer Prize for his book, The Emperor Of All Maladies: A Biography of Cancer