Roderick MacKinnon, a Professor of Molecular
Neurobiology and Biophysics at the Rockefeller University, was attracted
to scientific inquiry from his earliest years. As one of seven children
growing up in Burlington, Mass., outside Boston, he distinguished
himself from his siblings and friends by his love of solving puzzles.
This trait persists to this day and has driven him to tackle some
of the thorniest problems of neurobiology. Last year, MacKinnon
was praised by colleagues when he solved the molecular structure
of the potassium ion channel--an accomplishment hailed by Science
magazine as one of its "Breakthroughs of the Year," and described
in a commentary by a fellow scientist as "a remarkable achievement."
MacKinnon is acclaimed in his field for his penetrating ability
to make sense of technical information and bring it to a clear resolution
in his mind. "I've always been better at analysis than memorization,"
he says. He has always had a fascination observing the intricacies
of the natural world. He recalls as a boy wanting to go to summer
school because students were allowed to take home their own microscope--an
instrument MacKinnon eagerly put to use studying grass, leaves and
insects. "I loved watching the tiniest things swim and move," he
His interest in science did not waver as he grew older, and he
benefited from parents who did not attempt to steer him toward any
"I was never pressured into science or any other particular field
by my parents," he says. "All they expected was that we attend college
and then make the career decisions ourselves."
MacKinnon decided to attend nearby Brandeis University and majored
in biochemistry, receiving a B.A. in 1978. He moved on to study
medicine at Tufts University, securing his M.D. in 1982, and did
a residency at Beth Israel Hospital at Harvard Medical School.
In 1986, however, he abandoned his plans to practice medicine in
order to pursue postdoctoral studies back at Brandeis in the laboratory
of his undergraduate mentor Christopher Miller. "My scientific career
in effect began at the age of 30," he says. "My wife was very understanding
and supportive of my decision, given that it meant additional years
as a student rather than the financial stability a medical practice
MacKinnon also is very grateful to Miller for taking him under
his wing and helping him develop a fuller understanding in physics
and chemistry. "Chris Miller exemplified the spirit of science and
the approach to figuring out answers to very difficult questions,"
he says. "That is what attracted me to his laboratory and has guided
my scientific career."
Under Miller, MacKinnon began working on the biophysical aspects
of ion channel function. Shaped like tiny doughnuts floating in
oil, ion channels perform the dual functions of gateway and gatekeeper.
The holes in the doughnut form the gateway through which the ions
flow. However, these holes, or pores, are endowed with special properties
that enable different channel proteins to be selective as to which
ions they allow passage.
In Miller's lab and then in his own laboratory at Harvard Medical
School, MacKinnon sought to understand the structure of the protein
and the answers to two compelling questions: What do these channels
look like? And how are they able to allow passage of potassium ions
while blocking other ions that are similar?
Using electrophysiological and biochemical approaches at Harvard,
MacKinnon studied the interaction of the potassium channel with
a specific toxin derived from scorpion venom and figured out that
the toxin blocked the flow of ions by sitting directly on the pore
of the channel. He then exploited the toxin to analyze the subunit
structure, the moving gates and the ion conduction pathway of potassium
Upon realizing he needed a better understanding of structural biology,
MacKinnon moved to Rockefeller University in 1996 as a professor
and head of the Laboratory of Molecular Neurobiology and Biophysics.
Despite the expertise and insight he had gained at Brandeis and
Harvard, solving the channel structure was a daunting task-too daunting,
in the minds of some people.
"When I was at Harvard, friends and colleagues were telling me
it would take 10 years to figure out the ion channel structure,
but I was determined to try," MacKinnon says. "Rockefeller said
to me, in essence, that they like scientists who take risks and
they were willing to take me on in that attempt. It is nice when
an institution can offer that kind of support. In addition, it has
been tremendously helpful to my research to be able to confer with
the experts at Rockefeller in related fields."
At Rockefeller, MacKinnon learned X-ray crystallography, a skill
he realized he would need in order to directly visualize a potassium
channel in a way that previous experiments could not accomplish.
This newly acquired proficiency led to the first structure of the
potassium channel, which was published in Science in April
Many questions remain unanswered. MacKinnon suspects that ions
in the pore interact with one another through the structure of the
protein, but establishing this will require higher-resolution data.
The ability to actually look at ion channel structures has already
begun to stimulate new directions in ion channel research. His laboratory
recently solved the structure of the channel's Beta subunit, which
regulates when the channel opens and closes.
These new discoveries keep him fascinated and looking forward to
what lies ahead in the field he so enjoys. The occupation that he
finds so rewarding has recognized MacKinnon's contributions and
bestowed upon him some of its highest honors: MacKinnon is a member
of Alpha Omega Alpha Medical Honors Society, a PEW scholar in the
Biomedical Sciences and the recipient of the Mcknight Scholars Award,
the Biophysical Society Young Investigator Award, the Mcknight Investigator
Award, the W. Alden Spencer Award and the AAAS Newcomb Cleveland
"My belief is that if you do good science, science will take care
of you," he says. "If you tackle a problem and keep working on it,
eventually you will find some kind of outcome.