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
