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Rockefeller’s Roderick MacKinnon wins Nobel Prize in Chemistry
Physician, biophysicist and self-taught X-ray crystallographer becomes university’s 23rd Nobel laureate
BY LYNN LOVE and ZACH VEILLEUX
One of the ironies of being a Nobel Prize winning scientist is that few people understand what you do. Roderick MacKinnon, for example, Rockefeller’s newest Nobel laureate, who was awarded the 2003 prize in chemistry earlier this month, studies ion channels, a topic about which only a handful of people in the world can make cocktail party conversation.
When journalists showed up for MacKinnon’s October 8 press conference, the two-minute synopsis they were promised on his research quickly turned into a 30-minute seminar combining elements of mathematics, biology, physics, chemistry, neurology and molecular genetics.
The fact is, MacKinnon’s science is about as complicated as science can get. Yet it’s also among the most insightful research going on anywhere. Understanding ion channels is the key to understanding how nerves transmit information throughout the body. Every time your heart beats or your eyes blink, ion channels are at work.
Beginning in 1998, MacKinnon, who shares the $1.3 million prize with Peter Agre, a scientist at Johns Hopkins University School of Medicine in Baltimore, released a series of three-dimensional images of four structures that showed for the first time how this electrical signaling process occurs. In 2002 and 2003, he released images of the chemical- and voltage-dependent mechanisms that control the opening and closing of the channels.
Ion channels are tiny pores in the membranes of our cells that allow charged molecules called ions to pass in or out. Separate channels exist for potassium, calcium, sodium and chloride ions, which are each involved in, among other things, the process of moving electrical impulses between the brain and the rest of the body.
Going as far back as 1890, scientists had understood that the transfer of ions across the cell membrane was an essential activity for life-sustaining functions. In the 1920s, the existence of a narrow “ion channel” was proposed. In the 1950s, three British scientists discovered that ion transport in nerve cells produced an electrical signal that is conveyed from one cell to the next to transmit messages across the body. In order to do this, these channels would have to be able to admit one type of ion while keeping another out. Scientists knew they were there and knew what they did, but nobody had been able to visualize their structure or determine how they work.
Other molecular geneticists have collaborated with X-ray crystallographers in order to solve protein structures. The Massachusetts-born MacKinnon, exhibiting his typical independence and rigor, instead became a crystallographer himself (see “Impure Science,” below).
The images he’s published over the
last five years reveal not only the structure of ion channels, but also the filters that allow only the correct ions in and out of the channels. The chemistry of these filters provides a means of keeping an ion comfortable by creating a substitute for the water molecules that normally surround the ions. Because of the spacing between the oxygen atoms that make up this water substitute, only potassium ions can fit through the potassium ion selectivity filter (see illustration).
“We now can see that nature came up with a method for moving a signal that is elegant in its simplicity,” MacKinnon explains.
And elegance is just the beginning. Because of the role ion channels play in signaling processes, clinical researchers are very interested in MacKinnon’s work. The prognosis for heart arrhythmias, seizure disorders and other inherited and acquired electrical signaling diseases likely will improve in coming years as MacKinnon’s discoveries help doctors learn to remedy or prevent them.
When you win a Nobel Prize in chemistry, a man named Gunnar Öquist, secretary general of the Royal Swedish Academy of Sciences, phones very early in the morning. The prize is awarded at the sensible hour of 10 a.m., but in Sweden. For American scientists, that typically means a 5 a.m. phone call.
In MacKinnon’s case, Öquist was unable to get through either at home or at the office. That’s because MacKinnon was spending the week working from his vacation home on Cape Cod, Massachusetts; only his assistant knew how to reach him there.
It took some work to convince MacKinnon his early morning phone call was not a prank. Nevertheless, by 1:30 p.m., MacKinnon was back in New York and speaking at a press conference held in Caspary Auditorium on the Rockefeller University campus.
He spent the remainder of the day in one-on-one interviews and photo sessions with members of the media. All told, some 40 media outlets worldwide covered the news of MacKinnon’s prize — and at least several hundred others ran the newswire stories.
MacKinnon modestly calls his research “as basic as it gets,” but he has been well recognized for his accomplishments even before Sweden called. He was awarded the Albert Lasker Award for Basic Medical Research in 1999 and the Gairdner Award in 2001 and he was elected to membership in the U.S. National Academy of Sciences in 2000. MacKinnon received his B.A. from Brandeis University and his M.D. from Tufts University. He came to Rockefeller from Harvard in 1996.
“I was a very happy scientist at Harvard when I moved here, but Rockefeller has a very special feel, an environment where they only expectation on you is to concentrate on your work and discover things,” says MacKinnon. “This to me is a privileged existence, and I’m so indebted to Rockefeller for being what it is.”
Today MacKinnon heads the Laboratory of Molecular Neurobiology and Biophysics at Rockefeller and also is an investigator of the Howard Hughes Medical Institute. He is the 23rd scientist associated with Rockefeller University to be honored with the Nobel Prize. Eight current members of the Rockefeller faculty are Nobel laureates.

October 31, 2003



 

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