People
Good Genes
Building better corn - or helping Dad in a project to repair human proteins - is all in a day’s work
BY ANDREW VOWLES
He’d been retired for about two decades, but that didn’t stop Aser Rothstein from teaming up in the lab to pursue a promising idea with Prof. Steven Rothstein, Molecular and Cellular Biology. Now father and son run a company whose patented technology is intended to help prevent blood clotting, improve bone surgery and even reduce signs of aging. That’s rather a leap from Steven Rothstein’s day job at Guelph, where his busy plant genetics lab aims to find better ways to feed a growing world.
But the U of G professor says it’s all about science — and about having fun in the process. Science fun? Seated in the science complex atrium one morning this summer, Rothstein offers a shy smile. It’s like assembling a jigsaw puzzle, he says. Whether it’s helping plants use fertilizer more efficiently or making artificial human proteins, “you’re trying to figure out the best way to solve whatever puzzle you’re doing.”
This spring, his investigations into corn genetics received fresh funding worth $2.8 million from the Ontario Research Fund. Add in private and U of G funding over the next four years, and Rothstein and other researchers in his department and the Department of Plant Agriculture will receive more than $8.5 million to continue genomics studies of one of the world’s most important food crops.
Working with agricultural biotech company Syngenta, Rothstein is looking for genes that control plant growth. Using molecular and genetic tools to alter certain traits might make plants more efficient at absorbing and using nitrogen, he says.
That’s no small potatoes for Ontario corn producers, whose output is worth more than $1.5 billion a year. That market will only continue to grow, he says. Given expected population increases and the rising use of crops per person, we need to double corn yields over the next three to four decades, he says.
One key ingredient in that mix is nitrogen fertilizers. About half to two-thirds of fertilizer added to farmers’ fields is wasted, meaning economic losses and environmental pollution, says Rothstein.
“That’s not sustainable. Nitrogen fertilizers are one of the largest costs for farmers and are a very significant source of pollution from crop agriculture.”
The agricultural industry needs to use genetics technology to bump up ages-old plant-breeding practices and improve plants’ nitrogen use, he says.
He works on that puzzle with five graduate students and the same number of post-docs, three technicians and a research manager. Besides his science complex lab, that work takes place upstairs in the rooftop greenhouse and its special growth chambers, and in the crop science greenhouses.
To find his collaborator in a more recent project, head back downstairs and then southeast across campus and over Stone Road. Rothstein’s parents, Aser and Evelyn, live on the top floor of a condominium in the Village by the Arboretum retirement community.
Before moving to Guelph three years ago, they’d lived in Toronto since 1972, when Aser joined the Hospital for Sick Children as director of its research institute. A physiologist by training, he was recruited to help build up the hospital’s research arm.
Founded in 1954, the SickKids Research Institute is now the largest hospital-based research facility in Canada and one of the biggest worldwide. Funding comes from government agencies, the private sector and the SickKids Foundation, which was launched the year Aser arrived. Research, fundraising, administration: he was involved in all three, as well as holding appointments at the University of Toronto. He turned 65 in 1985 but stayed on for three more years.
A shelf in his home office holds a collection of blue hardbound volumes — some 300 research papers published during his career.
Aser earned an undergraduate degree at the University of British Columbia, then completed a doctorate in physiology at the University of Rochester in 1946. There he helped run the university’s piece of the Manhattan Project, the Second World War effort led by the United States to develop the first atomic bomb. The Rochester medical school had been named a national centre for studying health hazards of atomic research.
“We wrote the bible on protection against radioactive materials,” he says.
In his own research, Aser developed chemical probes to learn how uranium and mercury moved across membranes and how metals interfered with normal functioning of organs such as the kidney.
He stayed with Rochester’s atomic energy project after the war, and by the time he and Evelyn moved to Toronto, their three children were grown and entering university themselves. Aser says he never tried to direct his kids’ post-secondary schooling or careers. “None of my kids could you tell what to do,” he says. (Steven’s brother, David, is a microbiologist in Boston; their sister, Sharon, earned a master’s degree in psychology.)
Still, something rubbed off. “It had to be by osmosis,” says Aser. He had always stressed the idea of pursuing interesting and important work — the kind of thing he’d heard repeatedly from his own father, an immigrant who had fled Russia. “He was so proud when I became a scientist.”
Steven entered Swarthmore College in Pennsylvania planning to study history but was turned off by the first courses he encountered. Reverting to an abiding interest in science, he completed a chemistry degree.
By the time he did his PhD at the University of Wisconsin — where he met his wife, Carolyn — there was a new field opening up in molecular biology. He signed on to work with a professor on so-called “jumping genes” that can move around to different places in the genome.
He says his PhD supervisor was hands-off to an extreme, a situation that forced the grad student to figure out his own research project. That would turn out to be a key for Steven’s career.
“I realized I could be good at doing research. I basically initiated my project on my own. If it had all been laid out, I wouldn’t have had the same sense of confidence.”
He did a post-doctoral stint in plant genetics at the Plant Breeding Institute in Cambridge, England. Returning to the United States in 1978, he worked in agricultural biotechnology at Ciba Geigy in North Carolina. Geneticists were just developing tools to study genes and proteins, especially for use in improving crops.
“It was an exciting time in that field. The possibilities seemed boundless.”
Through a researcher he’d worked with in Toronto, Steven learned of an opening at Guelph. He arrived here in 1988 and later chaired the former Department of Molecular Biology and Genetics.
A decade later, he returned to industry, joining Pioneer Hi-Bred in Indiana to head research into agronomic traits — disease and insect resistance, drought tolerance — of crop plants. He ended up doing less research at Pioneer than he expected, however, and in 2002, he returned to Guelph.
“I was intrigued at the idea of coming back and starting over. There’s something exciting about being forced to start from scratch.”
Steven has taken that idea to an after-hours pursuit intended not to help feed the world but to repair it. Along with his father and two other colleagues, he’s running a biotech company developing a patented artificial version of a protein called elastin.
In the body, elastin lends flexibility to skin, joints, blood vessels and other tissues. That function degrades with age. The scientists have come up with a test-tube version intended to avoid triggering the body’s normal immune reaction, thus causing transplant rejection or blood clotting.
Elastin Specialties Inc. is now developing health applications, including coatings for cardiovascular devices, orthopedic materials, and even materials for repairing facial damage and reducing signs of aging such as wrinkles.
“The technology is really cool, and what we’re able to do with it is cool,” says Steven, who heads the company founded in 1996 and based in the MaRS Centre in downtown Toronto. He and his father work with Fred Keeley, a U of T biochemist and senior scientist at the SickKids Research Institute, and Kim Woodhouse, a tissue engineer and dean of the Faculty of Applied Science at Queen’s University.
Keeley had begun studying elastin and needed to learn about the biochemistry behind assembly of the protein. Recalls Aser: “I said, ‘I’ve got a son who knows all about proteins.’” After Steven manipulated the pertinent gene, they made the protein’s crucial parts in bacteria.
Referring to the administrative side of running a company, Steven says: “It’s been interesting to sit on the other side of the table. It’s been a great learning experience. And working with my dad has been nice.”
He allows that working together earlier in their careers might have posed a challenge. “Now we do it as colleagues and appreciate each other’s strengths. My dad is an outstanding scientist who thinks about things in the way that I do.”
Father and son also take the long view, whether it’s studying plants or human proteins.
“You can’t have miracles overnight,” says Steven. “You have to do very basic research.”
That’s a lesson he’s tried to impart to his own two children. Aaron just started medical school at the University of Western Ontario. Leah has finished pre-med courses at Harvard University and plans to apply to medical school this year.