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Sledge, George W. Jr., MD

doi: 10.1097/


It is October 31st as I write this, and despite my best intentions I have gone all month without putting pen to paper, if I may invoke two outdated technologies: will future generations look on pen and paper like my kids do eight-track cassettes?

By way of excuse, it has been a very distracting month: the baseball World Series (my Cardinals did not make it, losing out to the eventual winners, the Giants), Hurricane Sandy, the seemingly never-ending presidential campaign, and too much time spent in airports.

October's other annual ritual is the awarding of the Nobel prizes. I wrote about the prizes themselves last year (10/25/11 issue), and won't go over the same ground, but I always find the prizes to be a source of fascination. Some of the fascination is with the science (sometimes really cool, sometimes just esoteric to a non-specialist in chemistry and physics). But as often as not, what appeals about the prizes are the associated human stories.

This year is no different. Let's start with the Nobel Prize in Physiology or Medicine (it's formal title, though it has been a while since physiology won a medal), which went to John Gurdon and Shinya Yamanaka for their stem cell work. Gurdon's story is fascinating, both because of his path to science and because the science is so accessible.

Gurdon always wanted to be a scientist, but was explicitly discouraged by his teachers. A school report card called him quite probably the worst student his biology teacher had ever taught; the report went on to say: “I believe Gurdon has ideas about becoming a scientist; on his present showing this is quite ridiculous.”

The reason his teacher thought Gurdon had no future in the sciences reveals more about how science is taught than it does about Gurdon: he had an aversion to memorizing facts. How often do science teachers, at every level, mistake scientific facts for science, in the process turning their kids away from what should be the most fascinating of human endeavors? How often do the most creative lose out to the best rote memorizers? Aristotelian Scholasticism never really died: it just moved to high school.

So Gurdon focused on Greek and Latin until he went to Oxford, but it turned out that he stunk at the Classics as well, so he switched to science and thrived.

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The part of Gurdon's story that delights involves tadpoles. Tadpoles amazed me in my youth: that ability to change from fish to frog, right before your eyes, was wonderful, almost magical. Gurdon's Nobel Prize involves tadpoles, so I suspect he shared my child-like fascination with tadpole metamorphosis.

Gurdon won the Prize for work that he did fresh out of graduate school with a breathtakingly simple, and beautifully cool, experiment. He transplanted the cell nucleus from the intestinal cell of a mature frog into an empty egg cell of another. That cell then grew into a full formed, totally normal tadpole. Contra established dogma, specialized adult cells were not irreversibly committed, but retained the information required for embryonic development.

The experiment launched the stem cell revolution that continues today. Yamanaka received his prize for an extension of Gurdon's work, by demonstrating that the introduction of a suite of four genes into a mature cell could reprogram it into an embryonic stem cell.

It is still too early to know how the stem cell revolution will play out in medicine. The topic has been mired in politics and religion in the United States, unnecessarily so given the growing ability to reprogram adult cells. But it isn't too difficult to imagine a day in the near future where one goes in for a replacement heart reprogrammed from one's own keratinocytes, or perhaps a new lung. And give me, please, an infusion of reprogrammed neuronal tissues. And soon, please.

I always wonder whether anyone starts out thinking “I'll get a Nobel Prize for this experiment.” Reading Jim Watson's classic autobiography, The Double Helix, it certainly must be in the back (or front, in Watson's case) of some minds.

But I suspect that far more common are the Gurdons of the world, who look at tadpoles and wonder if they can re-create (almost in a Biblical sense) or comprehend Nature's wonders. One of my favorite science quotes comes from Isaac Newton, no slouch in the creativity department: “I was like a boy playing on the sea-shore, and diverting myself now and then finding a smoother pebble or a prettier shell than ordinary, whilst the great ocean of truth lay all undiscovered before me.”

Finding a smoother pebble or a prettier shell than ordinary is what working scientists do, of course: the great ocean of truth is simply too large, and too deep. You would drown in it if you tried to take it all in at once. Newtonian modesty is becoming.

Keith Campbell, the British cell biologist who cloned the first mammal (remember Dolly the sheep?) was also Gurdonesque, the kind of boy who “used to fill his mother's kitchen with frogs,” according to a newspaper report. Campbell died recently, within days of the announcement of Gurdon and Yamanaka's awards. Is a childhood passion for tadpoles a job requirement in the stem cell world? Just asking.

Nobel Laureates are frequently surprised when they get the call from Stockholm. Gurdon, on hearing that he was to get the Prize, asked, “Could it be someone is pulling your leg? That has happened before. … You have to be a little bit cautious.”

Gurdon's groundbreaking experiment was performed in 1962, so a man who has waited a half-century for a call from Sweden can be forgiven his caution. Only Peyton Rous's Prize had a longer latency period.

Brian Kobilka, who got this year's Chemistry Prize (for the biochemistry of cell surface receptors), said, “I thought it was some friends, initially. But I don't have friends that have a really good Swedish accent, so then I started believing it.”

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Economics Prize & Match Day

The Nobel Prize in Economic Sciences (some might argue that economic sciences is an oxymoron, but I won't quibble) appealed to the old medical student buried deep in my psyche. Remember Match Day, when you anxiously awaited your fate as a senior medical student? Would you get your first choice, that top Ivy League program? Or would you fail to match, and have to scramble for leftovers, humiliated in front of your classmates?

Match Day provoked immense paranoia in my class: we were all convinced that “the fix was in,” whatever that meant, and that our desires were secondary to those of the residency programs we were vying for (probably true).

Alvin Roth of Harvard and Lloyd Shapley of UCLA got the Economics Prize for their work in matching theory. Their work led to the development of efficient algorithms for matching supply and demand, algorithms now used (you guessed it) to match medical students to residency programs, and donor kidneys to transplant recipients. In fact, Roth designed the current matching program for residents, which went online in 1998.

Are today's students any less paranoid about the Match? I doubt it, but the Match is now based on Nobel Prize-winning work.

Lloyd Shapley is right up there with John Gurdon in the “dreams deferred” department. How many current Nobel Laureates received a Bronze Star for breaking Japanese military codes in World War II? Shapley is 89 years old, and worked at one time with fellow game theorist John Nash, of “A Beautiful Mind” fame. Nobel Laureates, as is common, cluster.

Once again, I did not get a call from Stockholm. But I will be patient. There's always next year. I'm not even close to 89, so what's the rush? And by the way, a Nobel Peace Prize to the European Union? Really? And you couldn't give me a call? What's the matter with you guys?

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