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Nobel winner followed his heart into research

When Roderick MacKinnon set up his new lab at Rockefeller University in 1996, only one graduate student volunteered to move with him from Harvard. His wife, a fellow chemist, felt so sorry for him that she agreed to help out with the research. Other colleagues thought he was wasting his time, trying something so difficult and so far from his area of expertise.

But in just two years, MacKinnon and his small X-ray crystallography lab were able to see into the inner workings of a cell in a way that had never been done before.

This month, MacKinnon, 47, was jointly awarded the Nobel Prize in Chemistry for his insights.

A native of Burlington who still maintains a home on Cape Cod, where he heard the news of his award, MacKinnon grew up examing bugs and blades of grass. He fondly remembers the summer he spent looking at pond water under a microscope.

"I was a daydreamer," said MacKinnon, who later moved to Cohasset. "Teachers kept telling me to pay attention."

He credits his high school gymnastics coach, Rick Hayes, for teaching him that he could accomplish "beautiful" things through hard work and discipline.

MacKinnon majored in biochemistry at Brandeis University, graduating in 1978. In his honors physics class, he met Alice Lee, and they were married in 1979. He also undertook a research project with a new professor, Christopher Miller, who would become his longtime mentor.

"Dr. Miller seemed to have so much fun. Being a research scientist seemed like a wonderful life," MacKinnon said.

Even though Miller advised him not to go into medicine -- "I knew he was made to be a research scientist" -- MacKinnon went to medical school at Tufts University.

After Tufts, MacKinnon did a residency at Beth Israel Hospital. "He was exceptional and was allowed to short-track into research in my cardiology laboratory," said Dr. James P. Morgan of Beth Israel. MacKinnon got a grant from the American Heart Association to study how the heart relaxes and contracts, which got him interested in potassium channels -- and on the path toward the Nobel.

The research taught him a larger lesson as well: He didn't want to be a doctor. "I realized that doctors don't get to the nuts and bolts of how little things actually work, which is what excites me," MacKinnon said. That excitement led him back to Miller for postdoctoral studies in biophysics at Brandeis (from which he was graduated in 1986), and then on to his own laboratory at Harvard Medical School, where he focused on molecular biology, particularly exploring potassium channels.

Potassium channels act as both gateways and gatekeepers on cell membranes, controlling the flow of ions and enabling brains to think, muscles to move, and hearts to beat. Malfunctioning ion channels contribute to epilepsy, arrhythmia, and other diseases.

But why did the channels admit potassium and nothing else?

He and other researchers explored the genes for the section of the channel that opens and closes like a pore in the cell membrane. Amazingly, every species on Earth has exactly the same instructions for that pore; nature thought it was the perfect solution. "How exactly did it work?" MacKinnon recalled wondering. "I couldn't solve that puzzle without seeing it."

So, he decided to learn X-ray crystallography, which produces three-dimensional images at the molecular level. The only trouble: He didn't have access to an X-ray crystallography lab.

Rockefeller heard of his plight and lured him away from his tenured job at Harvard with just such a lab. After two years of research, he was able to explain how the pore simulates the chemical and electrical forces of the ion's normal watery environment. "The ion thinks it's in water when it's in the pore," MacKinnon said. Other types of ions don't fit as snuggly in the pore, so they aren't enticed to enter.

MacKinnon's achievement opens up new directions in basic research, and it eventually may help fix problems with electrical signals in the brain.

"For the first time, we can see the most basic element of hardware in our brains," Miller said, "and it opens that up new directions in research."

Miller credits MacKinnon -- who shares the Nobel with Peter Agre of Johns Hopkins for separate research on other membrane channels -- for "betting the farm" on the research he wanted to do.

"Nobody else tried" this type of research, Miller said, "because it was so immensely overwhelming and would never work."

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