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

BRCA-1, a gene that strongly predisposes humans to breast and ovarian cancer.

By charting the life and death of leukemia cells as they responded to drugs in these mice, Skipper emerged with two pivotal findings. First, he found that chemotherapy typically killed a fixed percentage of cells at any given instance no matter what the total number of cancer cells was. This percentage was a unique, cardinal number particular to every drug. In other words, if you started off with 100,000 leukemia cells in a mouse and administered a drug that killed 99 percent of those cells in a single round, then every round would kill cells in a fractional manner, resulting in fewer and fewer cells after every round of chemotherapy: 100,000?1,000?10?and so forth, until the number finally fell to zero after four rounds. Killing leukemia was an iterative process, like halving a monster?s body, then halving the half, and halving the remnant half. Second, Skipper found that by adding drugs in combination, he could often get synergistic effects on killing. Since different drugs elicited different resistance mechanisms in cancer cells, using drugs in concert dramatically lowered the chance of resistance. Two drugs were therefore typically better than one; three drugs better than two. With several drugs and several iterative rounds of chemotherapy in rapid-fire succession, Skipper cured leukemias in his mouse model.

Cancer researchers knew that X-rays, soot, cigarette smoke, and asbestos represented vastly more common risk factors for human cancers.

Doctors treat diseases, but they also treat people, and this precondition of their professional existence sometimes pulls them in two directions at once.

Genes can certainly tell us about race, but can race tell us anything about genes? To answer this question, we need to measure how genetic variation is distributed across various racial categories. Is there more diversity within races or between races? Does knowing that someone is of African versus European descent, say, allow us to refine our understanding of their genetic traits, or their personal, physical, or intellectual attributes in a meaningful manner? Or is there so much variation within Africans and Europeans that intra-racial diversity dominates the comparison, thereby making the category African or European moot?

How many of us have asked the question, ?If this great country of ours can put a man on the moon why can?t we find a cure for cancer?

If someone were to draw a similar map of relationships among genes in a normal human cell, then proto-oncogenes and tumor suppressors such as ras, myc, neu, and Rb would sit at the hub of this cellular city, radiating webs of colored strings in every direction. Proto-oncogenes and tumor suppressors are the molecular pivots of the cell. They are the gatekeepers of cell division, and the division of cells is so central to our physiology that genes and pathways that coordinate this process intersect with nearly every other aspect of our biology. In the laboratory, we call this the six-degrees-of-separation-from-cancer rule: you can ask any biological question, no matter how seemingly distant?what makes the heart fail, or why worms age, or even how birds learn songs?and you will end up, in fewer than six genetic steps, connecting with a proto-oncogene or a tumor suppressor.

In 2006, the Vogelstein team revealed the first landmark sequencing effort by analyzing thirteen thousand genes in eleven breast and colon cancers. (Although the human genome contains about twenty thousand genes in total, Vogelstein?s team initially had tools to assess only thirteen thousand.) In 2008, both Vogelstein?s group and the Cancer Genome Atlas consortium extended this effort by sequencing hundreds of genes of several dozen specimens of brain tumors. As of 2009, the genomes of ovarian cancer, pancreatic cancer, melanoma, lung cancer, and several forms of leukemia have been sequenced, revealing the full catalog of mutations in each tumor type. Perhaps

In some nations, cancer will surpass heart disease to become the most common cause of death.

Is there something I can do to kill the cancer germ? Can the rooms be fumigated?? Should I give up my lease and move out?

Labs, too, can become machines. In science, it is more often a pejorative description than a complimentary one: an efficient, thrumming, technically accomplished laboratory is like a robot orchestra that produces perfectly pitched tunes but no music.

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

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.

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

Statistics, the journalist Paul Brodeur once wrote, are human beings with the tears wiped off.

The clinician, no matter how venerable, must accept the fact that experience, voluminous as it might be, cannot be employed as a sensitive indicator of scientific validity.

The language of cancer is grammatical, methodical, and even?I hesitate to write?quite beautiful. Genes talk to genes and pathways to pathways in perfect pitch, producing a familiar yet foreign music that rolls faster and faster into a lethal rhythm. Underneath what might seem like overwhelming diversity is a deep genetic unity. Cancers that look vastly unlike each other superficially often have the same or similar pathways unhinged. Cancer, as one scientist recently put it, really is a pathway disease.

The universe, the twentieth-century biologist J.B.S. Haldane liked to say, is not only queerer than we suppose, but queerer than we can suppose?and so is the trajectory of science.

This strategy?which cost Min Chiu Li his job?resulted in the first chemotherapeutic cure of cancer in adults.

What if?poring through Graham?s bank in some future era?the selected genius specimens were found to possess the very genes that, in alternative situations, might be identified as disease enabling (or vice versa: What if disease-causing gene variants were also genius enabling?)?

But another truth should be foremost in mind: that what we call nature today is a kinder, gentler, more depauperate world than at any time since at least the late Paleozoic, some 300 million years ago. Nature is not a temple but a ruin. A beautiful ruin, but a ruin all the same.

By now the perpetually changing landscape of breast cancer was beginning to tire him out. Trials, tables, and charts had never been his forte; he was a surgeon, not a bookkeeper.

Cancer thus exploits the fundamental logic of evolution unlike any other illness. If we, as a species, are the ultimate product of Darwinian selection, then so, too, is this incredible disease that lurks inside us.

Down to their innate molecular core, cancer cells are hyperactive, survival-endowed, scrappy, fecund, inventive copies of ourselves.

Genes cannot tell us how to categorize or comprehend human diversity; environments can, cultures can, geographies can, histories can. Our language sputters in its attempt to capture this slip. When a genetic variation is statistically the most common, we call it normal ? a word that implies not just superior statistical representation but qualitative or even moral superiority? When the variation is rare, it is termed a mutant ? a word that implies not just statistical uncommonness, but qualitative inferiority, or even moral repugnance. And so it goes, interposing linguistic discrimination on genetic variation, mixing biology and desire.

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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