Great Throughts Treasury

"Medicine, I said, begins with storytelling. Patients tell stories to describe illness; doctors tell stories to understand it. Science tells its own story to explain diseases."

"Memories sharpen the past; it is reality that decays."

"Min Chiu Li, the researcher who had been expelled from the institute for treating women with placental tumors with methotrexate long after their tumors had visibly disappeared."

"Modesty is a virtue, he would later write, yet one gets further without it."

"Most discoveries even today are a combination of serendipity and of searching."

"Most days, I go home and I feel rejuvenated. I feel ebullient."

"Movable tumors were typically early-stage, local cancers. Immovable tumors were advanced, invasive, and even metastatic."

"Mutant cells beget cells beget cells. A gene that increases the mobility of the cells is activated in a cell. This cell, having acquired motility, can migrate through the lung tissue and enter the bloodstream. A descendant of this mobile cancer cell acquires the capacity to survive in the bone. This cell, having migrated through the blood, reaches the outer edge of the pelvis, where it begins yet another cycle of survival, selection, and colonization. It represents the first metastasis of a tumor that originated in the lung. The man is occasionally short of breath. He feels a tingle of pain in the periphery of his lung. occasionally, he senses something moving under his rib cage when he walks. Another year passes, and the sensations accelerate. The man visits a physician and a CT scan is performed, revealing a rind-like mass wrapped around a bronchus in the lung. A biopsy reveals lung cancer. A surgeon examines the man and the CT scan of the chest and deems the cancer inoperable. Three weeks after that visit, the man returns to the medical clinic complaining of pain in his ribs and his hips. A bone scan reveals metastasis to the pelvis and the ribs. Intravenous chemotherapy is initiated. The cells in the lung-lining tumor respond. The man soldiers through a punishing regimen of multiple cell-killing drugs. But during the treatment, one cell in the tumor acquires yet another mutation that makes it resistant to the drug used to treat the cancer. Seven months after his initial diagnosis, the tumor relapses all over the body?in the lungs, the bones, the liver. On the morning of October, 17, 2004, deeply narcotized on opiates in a hospital bed in Boston and surrounded by his wife and his children, the man dies of metastatic lung cancer, a sliver of asbestos still lodged in the periphery of his lung. He is sixty-two years old."

"Never underestimate the power of? stupidity."

"New drugs appeared at an astonishing rate: by 1950, more than half the medicines in common medical use had been unknown merely a decade earlier. Perhaps even more significant than these miracle drugs, shifts in public health and hygiene had also drastically altered the national physiognomy of illness. Typhoid fever, a contagion whose deadly swirl could decimate entire districts in weeks, melted away as the putrid water supplies of several cities were cleansed by massive municipal efforts. Even tuberculosis, the infamous white plague of the nineteenth century, was vanishing, its incidence plummeting by more than half between 1910 and 1940, largely due to better sanitation and public hygiene efforts. The life expectancy of Americans rose from forty-seven to sixty-eight in half a century, a greater leap in longevity than had been achieved over several previous centuries."

"Most of the selected essays share a common thread: They describe how science happens."

"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."

"Negative genes, such as Rb, suppress cell division. In normal cells, these anti-oncogenes, or tumor suppressor genes, provide the brakes to cellular proliferation, shutting down cell division when the cell receives appropriate signals. In cancer cells, these brakes have been inactivated by mutations. In cells with missing brakes, to use Bishop?s analogy again, the stop signals for mitosis can no longer be registered. Again, the cell divides and keeps dividing, defying all signals to stop. Both abnormalities, activated proto-oncogenes and inactivated tumor suppressors (jammed accelerators and missing brakes), represent the core molecular defects in the cancer cell. Bishop, Knudson, and Varmus did not know how many such defects were ultimately needed to cause human cancers. But a confluence of them, they postulated, caused cancer."

"Mutations litter the chromosomes. In individual specimens of breast and colon cancer, between fifty to eighty genes are mutated; in pancreatic cancers, about fifty to sixty. Even brain cancers, which often develop at earlier ages and hence may be expected to accumulate fewer mutations, possess about forty to fifty mutated genes. Only a few cancers are notable exceptions to this rule, possessing relatively few mutations across the genome. One of these is an old culprit, acute lymphoblastic leukemia: only five or ten genetic alterations cross its otherwise pristine genomic landscape.* Indeed, the relative paucity of genetic aberrancy in this leukemia may be one reason that this tumor is so easily felled by cytotoxic chemotherapy. Scientists speculate that genetically simple tumors (i.e., those carrying few mutations) might inherently be more susceptible to drugs, and thus intrinsically more curable. If so, the strange discrepancy between the success of high-dose chemotherapy in curing leukemia and its failure to cure most other cancers has a deep biological explanation. The search for a universal cure for cancer was predicated on a tumor that, genetically speaking, is far from universal. In"

"Natures and features last until the grave."

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

"Never a cell biologist at heart, as a colleague recalled, he contaminated the cells, infected the cultures, and grew out balls of fungi in the petri dishes."

"Neither variant was morally or biologically superior; each was just more or less adapted to a particular environment."

"One swallow is a coincidence, but two swallows make summer."

"On that pea-size blue planet glimmering on the horizon, this was a moment of reckoning. It was a stunning scientific and intellectual accomplishment, Time reported in July 1969, for a creature who, in the space of a few million years?an instant in evolutionary chronology?emerged from primeval forests to hurl himself at the stars?. It was, in any event, a shining reaffirmation of the optimistic premise that whatever man imagines he can bring to pass."

"Oncologists and their patients are bound, it seems, by an intense subatomic force. So, albeit in a much smaller sense, this was a victory for me as well. I sat at Carla?s table and watched her pour a glass of water for herself, unpurified and straight from the sink. She glowed radiantly, her eyes half-closed, as if the compressed autobiography of the last five years were flashing through a private and internal cinema screen. Her"

"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"

"Normalcy is the antithesis of evolution."

"On August 7, 1945, the morning after the Hiroshima bombing, the New York Times gushed about the extraordinary success of the Project: ?University professors who are opposed to organizing, planning, and directing research after the manner of industrial laboratories? have something to think now. A most important piece of research was conducted on behalf of the Army in precisely the means adopted in industrial laboratories. End result: an invention was given to the world in three years, which it would have taken perhaps half-a-century to develop if we had to rely on prima-donna research scientists who work alone?. A problem was stated, it was solved by teamwork, by planning, by competent direction, and not by the mere desire to satisfy curiosity."

"Once again, Bradford Hill, the eminence grise of epidemiology, proposed a solution to this impasse. For studies on chronic and complex human diseases such as cancer, Hill suggested, the traditional understanding of causality needed to be broadened and revised. If lung cancer would not fit into Koch?s straitjacket, then the jacket needed to be relaxed. Hill acknowledged epidemiology?s infernal methodological struggle with causation?this was not an experimental discipline at its core?but he rose beyond it. At least in the case of lung cancer and smoking, he argued, the association possessed several additional features: It was strong: the increased risk of cancer was nearly five- or tenfold in smokers. It was consistent: Doll and Hill?s study, and Wynder and Graham?s study, performed in vastly different contexts on vastly different populations, had come up with the same link. It was specific: tobacco was linked to lung cancer?precisely the site where tobacco smoke enters the body. It was temporal: Doll and Hill had found that the longer one smoked, the greater was the increase in risk. It possessed a biological gradient: the more one smoked in quantity, the greater was the risk for lung cancer. It was plausible: a mechanistic link between an inhaled carcinogen and a malignant change in the lung was not implausible. It was coherent; it was backed by experimental evidence: the epidemiological findings and the laboratory findings, such as Graham?s tar-painting experiments in mice, were concordant. It behaved similarly in analogous situations: smoking had been correlated with lung cancer, and also with lip, throat, tongue, and esophageal cancer. Hill used these criteria to advance a radical proposition. Epidemiologists, he argued, could infer causality by using that list of nine criteria. No single item in that list proved a causal relationship. Rather, Hill?s list functioned as a sort of a la carte menu, from which scientists could pick and choose criteria to strengthen (or weak) the notion of a causal relationship. For scientific purists, this seemed rococo?and, like all things rococo, all too easy to mock: imagine a mathematician or physicist choosing from a menu of nine criteria to infer causality. Yet Hill?s list would charge epidemiological research with pragmatic clarity. Rather than fussing about the metaphysical idea about causality (what, in the purest sense, constitutes cause?), Hill changed its emphasis to a functional or operational idea. Cause is what cause does, Hill claimed. Often, like the weight of proof in a detective case, the preponderance of small bits of evidence, rather than a single definitive experiment, clinched cause."

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

"Nineteenth-century doctors often linked cancer to civilization: cancer, they imagined, was caused by the rush and whirl of modern life, which somehow incited pathological growth in the body. The link was correct, but the causality was not: civilization did not cause cancer, but by extending human life spans?civilization unveiled it."

"One leukemia doctor wrote, I know the patients, I know their brothers and sisters, I know their dogs and cats by name.? The pain is that a lot of love affairs end."

"Our encounter with cancer has rounded us off; it has smoothed and polished us like river rocks."

"Patients tell stories to describe illness; doctors tell stories to understand it. Science tells its own story to explain diseases."

"Penicillin, that precious chemical that had to be milked to its last droplet during World War II (in 1939, the drug was re-extracted from the urine of patients who had been treated with it to conserve every last molecule), was by the early fifties being produced in thousand-gallon vats. In 1942, when Merck had shipped out its first batch of penicillin?a mere five and a half grams of the drug?that amount represented had been half of the entire stock of the antibiotic in America."

"Probably the most important reason we are seeing more cancers than before is because the population is ageing overall. And cancer is an age-related disease."

"Portions of this interview first appeared in OncNurse magazine in February 2011. We are grateful to Christin Melton for her questions."

"Pierre and Marie (then Maria Sklodowska, a penniless Polish immigrant living in a garret in Paris) had met at the Sorbonne and been drawn to each other because of a common interest in magnetism."

"Pharmacology is benefited by the prepared mind. You need to know what you are looking for."

"Radiation can be used to control or palliate metastatic tumors in selected cases, but is rarely curative in these circumstances."

"Postwar U.S. was the world's leader in science and technology. The investment in science research was staggering."

"Prostate cancer represents a full third of all cancer incidence in men?sixfold that of leukemia and lymphoma."

"Resistance to provide palliative care to patients was so great that doctors did not even looked in the eye when we recommended them to stop work to save lives and begin to save the dignity ... doctors were allergic to the smell of death. Death meant failure, defeat , was the death of them, the death of medicine, oncology death."

"Sandeep Jauhar?s Doctored is a passionate and necessary book that asks difficult questions about the future of medicine. The narrative is gripping, and the writing is marvelous. But it was the gravity of the problem?so movingly told?that grabbed and kept my attention throughout this remarkable work."

"Science begins with counting. To understand a phenomenon, a scientist must first describe it; to describe it objectively, he must first measure it."

"Recombinant DNA technology allowed Genentech to synthesize human proteins de novo: rather than extracting proteins from animal and human organs, Genentech could ?engineer? a human gene into a bacterium, say, and use the bacterial cell as a bioreactor to produce vast quantities of that protein. The technology was transformative. In 1982, Genentech unveiled the first ?recombinant? human insulin; in 1984, it produced a clotting factor used to control bleeding in patients with hemophilia; in 1985, it created a recombinant version of human growth hormone?all created by engineering the production of human proteins in bacterial or animal cells."

"Science is often described as an iterative and cumulative process, a puzzle solved piece by piece, with each piece contributing a few hazy pixels of a much larger picture. But the arrival of a truly powerful new theory in science often feels far from iterative. Rather than explain one observation or phenomenon in a single, pixelated step, an entire field of observations suddenly seems to crystallize into a perfect whole. The effect is almost like watching a puzzle solve itself."

"Scientists often study the past as obsessively as historians because few other professions depend so acutely on it. Every experiment is a conversation with a prior experiment, every new theory a refutation of the old."

"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."

"Second, proto-oncogenes and tumor suppressor genes typically lie at the hubs of cellular signaling pathways."

"Scientists divide. We discriminate. It is the inevitable occupational hazard of our profession that we must break the world into its constituent parts -- genes, atoms, bytes -- before making it whole again. We know of no other mechanism to understand the world: to create the sum of its parts, we must begin by dividing it into the parts of the sum."

"Something akin to this process, a few researchers believe, is constantly occurring in cancer?at at least in leukemia. In the mid-1990s, John dick, a Canadian biologist working in Toronto, postulated that a small population of cells in human leukemias also possess this infinite self-renewing behavior. These cancer stem cells act as the persistent reservoir of cancer?generating and regenerating cancer infinitely. When chemotherapy kills the bulk of cancer cells, a small remnant population of these stem cells, thought to be intrinsically more resistant to death, regenerate and renew cancer, thus precipitating the common relapses of cancer after chemotherapy. Indeed, cancer stem cells have acquired the behavior of normal stem cells by activated the same genes and pathways that make normal stem cells immortal?except, unlike normal stem cells, they cannot be lulled back into physiological sleep. 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 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."

"Should I refuse my dinner because I don?t understand the digestive system?"

"Soot is a mixture of chemicals that would eventually be found to contain several carcinogens."