Separate research paths lead to a lifelong partnership
Oliver Smithies and Nobuyo Maeda were born in island countries half a world apart – he in England, she in Japan – but each in their own way found a path to a life in science.
Their individual paths took them to the United States and the University of Wisconsin at Madison, where they eventually found each other.
When Maeda was unable to secure a faculty position there in 1988, Smithies urged her to apply to other research universities. Wherever she went, he told her, he would follow.
That was when two paths became one. And they followed it to Carolina.
It is here, in the sprawling lab that takes up the entire seventh floor of the Brinkhous-Bullitt Building, that they have built a life together around a never-ending pursuit of their research and the contentment they share in that quest.
It is serious work, but Smithies often does it with the same sense of play he had as a curious little boy tinkering with things to see how they worked.
Nothing else he has done – not even taking his beloved glider high into the clouds – has filled him with as much wonder or unbridled joy. Maybe that it is why, even as he approaches 60 years on the bench, he and Maeda choose to come to work even on weekends.
“An interesting thought is, ‘Where is your home?’ Well, my home is on Umstead Drive about a mile and a half from here, but really it isn’t,” Smithies said. “This is my home. This is where I’m most comfortable. I’m most relaxed and enjoying myself when doing experiments.”
It is a restful, almost peaceful occupation, said Smithies, who nearly six years ago, at the age of 82, became the first and only Carolina faculty member to win a Nobel Prize.
The science of snakes
Maeda was born in Sendai, Japan, in the early 1950s around the time Smithies came to the U.S. to do postdoctoral work with J.W. “Jack” Williams, a learned physical chemist at Wisconsin.
Smithies’ doctoral adviser at Oxford University, A.G. “Sandy” Ogston, had passed along to Smithies his fascination with the application of physical chemistry to biological problems. It was also Ogston who insisted that Smithies go to the States.
“Actually, I wasn’t very keen,” Smithies said. “I remember saying, ‘I don’t care much for Americans,’ and he said, ‘That’s all the more reason you should go.’”
It was a Rhodes scholar in Ogston’s lab who talked Smithies into applying for a visiting fellowship to go to Wisconsin, his home state. Although Smithies wasn’t initially selected for the fellowship, he came because the person selected had tuberculosis and couldn’t get a visa – and Smithies was next in line.
After completing his postdoctoral work at Wisconsin, Smithies went to the Connaught Medical Research Laboratory, where he worked for eight years before returning to Wisconsin as a faculty member in 1960.
Maeda followed a different path to Wisconsin.
For most of her early life, her most influential adviser was her father, a professor in chemical engineering who saw no reason why Maeda – the middle of his three daughters – needed to go away to college at all.
“I was born in Sendai and I was brought up in Sendai and my whole education, up through my Ph.D., was in Sendai,” Maeda said. “My father was a very traditional person and he said, ‘Sendai has a good university. There is no reason for a woman to go somewhere else to get an education.’”
As a little girl, she knew she wanted to conduct research using her hands, and that led her to pursue chemistry at Tohoku University.
She ended up studying snakes because she showed up late for the meeting in which students picked study topics for a biochemical laboratory. “I was two minutes late, but by then my fellow students had all picked their topics and there was only one left,” Maeda said. “That is how I ended up working on sea snake venom. Toxins.”
The chance assignment grew into a fascination with molecular evolution and what she could find studying the amino acid sequences of different sea snakes around the world.
It was in pursuit of that knowledge that Maeda left her parents’ home in 1978 and headed for Wisconsin to do postdoctoral work in the physiological chemistry lab of Walter Fitch, an expert on the subject. It was the first time she had lived on her own, away from her family.
She was shocked that most of the equipment in the lab was so old. “I found out later that much of the equipment we were using were castoffs from Oliver’s laboratory when he used to work in protein chemistry,” Maeda said.
Had she already been married to him that would have been no surprise. “He doesn’t like to throw anything away,” she said.
Reagan’s invisible hand
Some couples believe God or fate brings them together. Smithies and Maeda credit former President Ronald Reagan.
By fall 1980, Maeda had won an appointment to the National Institutes of Heath in Washington D.C., but on Jan. 20, 1981, Reagan ordered an across-the-board hiring freeze on all federal employees in the executive branch, which includes the NIH.
“So in one day I lost my appointment,” Maeda said. “I couldn’t move.”
That’s when Smithies got a call from Fitch to explain Maeda’s situation and to ask if he could find a place for her.
“Walter said, ‘She is a very nice Japanese lady and she will listen to you very carefully and politely, but then she will do what she wants to do,” Smithies recounted. “That was a good sign, I thought, and so she came.”
Maeda believes it was being around each other so much that drew them together. “I work all the time – Saturday, Sunday and late into the evening – and Oliver is in the lab most of the time, so it was quite natural that we started to talk,” she said.
Smithies says simply, “You know how these things happen. People fall for each other.”
Soon after Maeda joined his lab, she began using the process of homologous recombination that Smithies and fellow scientist Mario Capecchi had begun experimenting with to target genes in mice.
“I thought it would be a very good idea to make a model of human disease with mice using Oliver’s techniques,” she said.
In the years since, Maeda has focused on understanding gene-gene and gene-environment interactions in complex human diseases such as atherosclerosis, hypertension and diabetes.
Smithies’ ‘runway moment’
In 1975, as Smithies turned 50 and his first marriage was ending, he took up flying lessons. “I no longer had lawns to mow, so I thought I’d go out and learn flying,” he has often joked.
Ten years later, on the morning of May 18, 1985, that same exhilaration of flying came over him as he had the burst of insight that would later win him the Nobel Prize.
As Smithies stood in a pitch-black darkroom developing the X-ray film that would prove whether his experiment of molecular manipulation had succeeded or failed, he experienced the same emotion he felt up in the clouds, flying with only a panel of instruments to guide him.
If everything is done right, when you come out of the clouds, the runway is there, he said. When Smithies turned on the light, the X-ray film revealed 10 black lozenge-shaped bars, all in a straight line. Away from the others was what he was looking for – the 11th bar showed that his target gene had been altered, exactly as he had predicted. That, as Smithies later told his fellow scientists at a meeting, “was his runway moment.”
‘A school for social living’
Maeda had received three job offers – one in California, one in Chicago and the one in Chapel Hill.
Even when they arrived here, there was a recognition that the groundbreaking work Smithies had done in homologous recombination might earn him a Nobel. But as the years passed, he began to doubt the day would ever come.
“When I got that proverbial phone call from Stockholm this morning, there was rather a feeling of peace,” Smithies said at the news conference the same day that he received the call – Oct. 8, 2007. He also said that he hoped the award would not change his life. “I rather enjoy it as it is,” Smithies said. “If it isn’t broken, don’t fix it.”
In June, Smithies celebrated his 88th birthday, and his life and work with Maeda remains remarkably unchanged – and unbroken.
What being a scientist means, Smithies said, is typed on a piece of paper he has carried in his wallet for longer than he can remember. It’s what his mentor, the late Ogston, told him in his youth.
“For science is more than the search for truth, more than a challenging game, more than a profession. It is a life that a diversity of people lead together, in the closest proximity, a school for social living. We are members one of another.”
The video about Smithies’ passion for his work was shot by Crystal Beal from News Services and edited by Gary Moss from the University Gazette, with assistance from Rob Holliday from News Services and Mary Lide Parker from Research Communications. Patty Courtright from the University Gazette conducted the interview.