Siddhartha Mukherjee

Siddhartha
Mukherjee
1970

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

Author Quotes

Is medicine a science?

Its false-positive and false-negative rates make it far from an ideal screening test. But the fatal flaw in mammography lies in that these rates are not absolute: they depend on age. For women above fifty-five, the incidence of breast cancer is high enough that even a relatively poor screening tool can detect an early baseline tumor and provide a survival benefit. For women between forty and fifty years, though, the incidence of breast cancer sinks to a point that a mass detected on a mammogram, more often than not, turns out to be a false positive. To use a visual analogy: a magnifying lens designed to make small script legible does perfectly well when the font size is ten or even six points. But then it hits a limit. At a certain size font, chances of reading a letter correctly become about the same as reading a letter incorrectly.

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

Normalcy is the antithesis of evolution.

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.

Src was a prototypical kinase?although a kinase on hyperdrive. The protein made by the viral src gene was so potent and hyperactive that it reflexively phosphorylated anything and everything around it, including the antibody that Erikson had used to bind it. Src worked by unleashing a volley of phosphorylation?throwing on dozens of molecular switches. In src?s case, the activated series of proteins eventually impinged on proteins that controlled cell division. Src thus forcibly induced a cell to change its state from non-dividing to dividing, ultimately inducing accelerated mitosis, the hallmark of cancer.

The children and grandchildren of famine-starved individuals tended to develop metabolic illnesses, as if their genomes carried some recollection of their grandparents? metabolic travails.

The landscape of carcinogens is not static either. We are chemical apes: having discovered the capacity to extract, purify, and react molecules to produce new and wondrous molecules, we have begun to spin a new chemical universe around ourselves. Our bodies, our cells, our genes are thus being immersed and re-immersed in a changing flux of molecules--pesticides, pharmaceutical drugs, plastics, cosmetics, estrogens, food products, hormones, even novel forms of physical impulses, such as radiation and magnetism. Some of these, inevitably, will be carcinogenic. We cannot wish this world away; our task, then, is to sift through it vigilantly to discriminate bona fide carcinogens from innocent and useful bystanders.

The trial designed to bring the most rigorous statistical analysis to the cause of lung cancer barely required elementary mathematics to prove its point.

This seminal transition from descriptive biology to the functional biology of cancer will provoke three new directions for cancer medicine. The first is a direction for cancer therapeutics. Once the crucial driver mutations in any given cancer have been identified, we will need to launch a hunt for targeted therapies against these genes. This is not an entirely fantastical hope: targeted inhibitors of some of the core thirteen pathways mutated in many cancers have already entered the clinical realm. As individual drugs, some of these inhibitors have thus far had only mild response rates. The challenge now is to determine which combinations of such drugs might inhibit cancer growth without killing normal cells.

We tend to think of cancer as a modern illness because its metaphors are so modern. It is a disease of overproduction, of fulminant growth?growth unstoppable growth, tipped into the abyss of no control. Modern biology encourages us to imagine the cell as a molecular machine. Cancer is that machine unable to quench its initial demand (to grow) and thus transformed into an indestructible, self-propelled automation. The notion of cancer as an affliction that belongs paradigmatically to the twentieth century is reminiscent, as Susan Sontag argued so magisterially in her book Illness as Metaphor, of another disease once considered paradigmatic of another era: tuberculosis in the nineteenth century. Both diseases, as Sontag pointedly noted, were similarly obscene?in the original meaning of that word: ill-omened, abominable, repugnant to the senses. Both drain vitality; both stretch out the encounter with death; in both cases, dying, even more than death, defines the illness.

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.

First Name
Siddhartha
Last Name
Mukherjee
Birth Date
1970
Bio

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