A Humble Scientist Gets the Proverbial Phone Call

Oliver Smithies took some time out Sunday to fly his motor glider (he also spent some time in the lab, not an atypical weekend activity). It was an uneventful day, as the winds were light and he couldn’t gain altitude.

The “up-current,” as he calls it, blew in early Monday morning. The “proverbial phone call from Stockholm” found him in the bed. Years of trying to get laboratory mice to tell us how to manipulate genes to create new therapies for disease had resulted in a Nobel Prize in medicine. (See main story, “The First Nobel: Oliver Smithies’ Work Pays Off.”)

It was not totally unexpected. Smithies and his collaborators in Utah and in Wales had been honored for this work before. They won the Lasker Award, sometimes known as the “American Nobel” in 2001. Whatever publicity that might have followed that was usurped instantly: It happened on Sept. 11, 2001.

Nothing that had happened by mid-afternoon on the big day had worn down any of his humbleness, nor dulled his quick humor. Dressed in the same khakis and plaid shirt, sleeves rolled up past the elbows, that he might wear any day to the lab, he was patient with a room full of reporters who weren’t quite sure what to ask this master of such complicated science.

“I actually feel rather peaceful about it,” he told the gathering. (He hadn’t even had time to talk to his co-winners.) Then he launched effortlessly into the everyman’s explanation of the genetic code: “A book with 1,000 pages, 1,000 letters on every page, more than 1,000 of these books …”

The 82-year-old with a full crop of minimally coifed white hair put the trio’s work into a brief timeline. In 1985, he published the paper that showed it was possible to alter the genetic code. Mario Capecchi simplified the process — they began to think not in terms of how to make something happen but how to keep something from happening. Martin Evans figured out how to “make” a mouse that replicated human disease.

The work that followed in mouse modeling was centered in Chapel Hill.

You knock out a gene and see what it gets you, he explained. You knock out a little light bulb, and you can’t read the newspaper at night. You knock off a wheel, and the car won’t run.

At Carolina, Smithies applied mouse modeling to cystic fibrosis research that already was under way. He also turned his methods on the mysteries of hypertension, work that still is going on in his lab. He’s still there full time and plenty of weekends. He said he felt a little guilty that he’d been exempted from administrative duties — scientists who must go that route, he said, often sacrifice what could be important research.

After 30 years of working with graduate students, he stopped that when he came to Chapel Hill 19 years ago, now employing only post-docs. Several of them showed up to applaud him Monday. “I told them they’d all be fired if they didn’t come,” he laughed.

At a reception in his honor in the atrium lobby of the Lineberger Comprehensive Cancer Center, with well-wishers smiling from two balconies above, the noted breast cancer researcher Etta Pisano, Kenan Professor of radiology and biomedical engineering, anticipated that Smithies would repeat what he’d told the media: No, he couldn’t cite specific medical breakthroughs that followed from his work — there just hasn’t been enough time yet.

Pisano said the mouse modeling work would “lead to new therapies in virtually every disease that has a genetic basis.” She added that was not an overstatement.

The honoree, whom The New York Times referred to in 1995 as “a scientific phenomenon, a man whose intellectual pace has continued unabated for half a century,” told the crowd that one of his favorite accolades was the North Carolina Award, given to people who serve the state from the tops of their fields. He said he’d be content to die at the laboratory bench.

He seemed most at peace when he told the reporters, “Someone will improve on this, and it will become old-fashioned.”

Related coverage is available online:

  • Of Mice and Man: The human genome is complete. Now medical schools will subdivide the vast field of genetics research. Carolina is making a major investment to strengthen its specialty in genetic engineering.
    Cover story from the November/December 2000 issue of the Carolina Alumni Review, available online to Carolina Alumni members.
  • Accompanying profile, detailing Smithies’ work, also in the November/December 2000 issue of the Carolina Alumni Review.

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