Tufts medical alumnus wins Nobel in chemistry

Dr. Roderick MacKinnon, a 1982 graduate of Tufts School of Medicine whose research explains the electrical activity that underlies all movement, sensation and thought, is the winner of the 2003 Nobel Prize in Chemistry.

A professor and head of the Laboratory of Molecular Neurobiology and Biophysics at Rockefeller University, MacKinnon, 47, shares the $1.3 million prize with Dr. Peter Agre of Johns Hopkins School of Medicine.

Dr. Roderick MacKinnon

A self-taught X-ray crystallographer, MacKinnon’s exquisitely detailed portraits of a class of proteins explain the generation of nerve impulses. These proteins, called ion channels, are tiny pores that stud the surface of all of our cells and allow the passage of potassium, calcium, sodium and chloride molecules called ions. Rapid-fire opening and closing of these channels release ions, moving electrical impulses from the brain in a wave to their destination in the body.

Inherited and acquired defects of ion channels interfere with proper electrical signaling and can be fatal. The prognosis for cystic fibrosis, heart arrhythmias 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.

MacKinnon’s “successful exploitation of crystallography signals the dawning of a new era in the study of ion channels and the diseases associated with them,” said Rockefeller President Paul Nurse, himself a Nobel laureate. “His discoveries are of astonishing clarity and significance.”

His path to the Nobel was slightly less clear.

MacKinnon was worried about finding a job when he graduated from Brandeis University with a B.A. in biochemistry in 1978. “I think I went to medical school because everybody else was doing it,” he says.

His mentor at Brandeis, Dr. Christopher Miller, recalls advising his star pupil against the move. “He was obviously off-scale from the beginning,” Miller says. “He had this wonderful blend of naiveté and sweetness and an immense intellect. So in the middle of his senior year I said to him, ‘Listen, Rod, don’t go to med school.’ And he told me, ‘You know, I like science but don’t feel confident enough about my future there. I really think I need a medical degree.’ ”

Making a huge contribution to medical research wasn’t part of his thinking. But the combination of iron discipline and a voracious intellectual appetite that MacKinnon cultivated during his time at Tufts School of Medicine gave him the tools he would later need to tackle some of the most baffling problems in molecular neurobiology.

In 1986, for example, when he returned to Brandeis on a postdoctoral fellowship in biochemistry, MacKinnon says he felt “way behind” in the field and began devouring material to catch up. Says Miller about his friend and colleague, “He had, and has, an amazing ability to focus—to have his intuition lead him to the most important, central question.”

A view of the potassium channel structure, with the sphere at the center representing a potassium ion in motion through the channel.

MacKinnon’s fame within the field grew. By 1989, he had his own lab at Harvard Medical School, where he was exploring the mysterious life of ion channels—those specialized protein molecules in cell membranes that play a critical role in the body’s electrical system. He had two questions: What do ion channels look like? And how are these channels, sorting ions at a rate of one million per second, able to allow the passage of electricity-bearing potassium ions while blocking other similar ions? No one knew the answer to either question.

To advance his research, MacKinnon decided he needed to master X-ray crystallography. By reading books and picking the brains of his peers, in short order he taught himself a technique that normally would require years of specialized training. In 1996, he left his post as a full professor at Harvard for Rockefeller University. Within a year or two, MacKinnon had produced the world’s first glimpse of a potassium ion channel—considered the Holy Grail of bioelectricity. The image appeared in the April 1998 issue of Science. “We now can see that nature came up with a method for moving a signal that is elegant in its simplicity,” MacKinnon said at the time.

In fall 1999, MacKinnon won the Albert Lasker Basic Medical Research Award for his work, a distinction that places him among the elite scientists of the past half-century. The Lasker prizes were established in 1946 and are often called “America’s Nobels.” More than half of all Lasker winners since 1962 have gone on to win the Nobel Prize.

MacKinnon believes his research into ion channels will pave the way for the creation of more precisely targeted, hence more effective, pharmaceuticals. His maverick approach paid off because he is not, and never has been, content with halfway measures. “I think we shouldn’t be just shooting to survive,” he says. “We should be shooting to try and make a difference. Go for it. I think if you crash and burn trying, it’s still going to be better than if you never tried at all.”

He gave the same advice to graduates of Tufts’ medical and Sackler schools during his commencement address in 2002, when Tufts awarded him an honorary degree: “If you develop a fascination, hear a little voice inside telling you to take a road that was not anticipated, don’t be afraid to listen to the voice and follow the road. Whether that voice is pointing you to a career change that is different from what you had planned, or telling you to take an unconventional approach within a discipline, don’t be afraid to take a chance. What is most important is that you find your passion and pursue it.”

Portions of this story were excerpted from the cover story of the spring 2002 issue of Tufts Medicine that was written by Bruce Morgan, the magazine’s editor.