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‘He just had an abiding love of research, whether thinking about it, doing it, talking about it or facilitating others to do it,’ Steven Rothstein says of his father.

Aser Rothstein became a top physiologist and cell specialist by way of pique. His university physics professor wasn't impressed when he was often late for the early morning class, and deployed a series of caustic remarks to predict that his sleepy student would surely receive a BAC ("Bounced at Christmas") degree. Instead, the student wrote a perfect exam in his first semester, scored 94 per cent on his final and was invited by the now-friendly professor to major in physics.

"Although I liked physics, largely to spite him, I announced in triumph that I planned to major in biology," Dr. Rothstein later wrote in his memoirs. "Thus, my major career decision was made in about 30 seconds, on impulse, to spite a professor."

Dr. Rothstein at first regretted his move, as physics crested during the Atomic Age. Young physicists worked on great things and received full professorships. Biologists were lucky to have a job. But in the long run, it was biology that bloomed, and Dr. Rothstein was swept along in its tide. His earlier decision, he would realize, was "both rational and clever."

Globally, Dr. Rothstein achieved renown for his contributions to the fields of cellular physiology and toxicology. In Canada, he made his mark as director for 14 years of the Research Institute at Toronto's Hospital for Sick Children, which he grew to one of the premier pediatric research establishments in the world.

His own research focused on cells, specifically how and why the plasma membranes that encase cells allow certain substances to pass through, but not others. Membrane research has important implications for a host of issues, including cancer and organ transplants, and genetic diseases such as cystic fibrosis and muscular dystrophy.

One of his notable achievements, in the late 1960s, was to identify the protein responsible for anion transport in red blood cells (an anion is a negatively charged ion). With pioneering experiments using radioisotopes, he found a chemical that would bind to a specific molecule, and, using radioactivity, separated all the proteins from the red cells, finding the one responsible for anion transport.

"It was really the first functional membrane molecule to be identified," Sergio Grinstein, who was a post-doctoral fellow in Dr. Rothstein's lab beginning in 1976 and is now a senior scientist at the Hospital for Sick Children Research Institute, said. Until the discovery, "nobody had any way of knowing what molecule was responsible for a specific transport function. He was able to identify, for the first time, a membrane protein that transports something."

Dr. Rothstein was a passionate researcher. He wrote some 300 papers in his lifetime, and the title of his memoir is My Love Affair With Membranes.

"He just had an abiding love of research, whether thinking about it, doing it, talking about it or facilitating others to do it," his son Steven Rothstein, a professor of molecular and cellular biology at the University of Guelph, said. "When I was growing up, he would bring famous scientists home for dinner and he'd just be talking with them. We wouldn't know what was going on, [but] you could tell he just really had a passion."

His love of research was rooted in curiosity. "If you know what's going to happen, you don't have to do the research," the elder Dr. Rothstein reasoned to an interviewer in 1986.

Aser Rothstein died in Guelph, Ont., on July 4 at the age of 97.

He was born in Vancouver on April 29, 1918. His father, Sam, had been smuggled out of prerevolutionary Russia at the age of 16 to join an older brother in New York. His mother, Etta (née Wiseman), had emigrated from the Austro-Hungarian Empire. The family ran several businesses, including trading in scrap metal and selling burlap bags.

Their son earned his spite-fuelled undergraduate degree in biology at the University of British Columbia, set his sights on becoming a professor and completed graduate work at the University of California at Berkeley and the University of Rochester, in New York. His first project, undertaken while he was a doctoral student, was to learn how humans could adapt to extreme heat and dehydration, as a prelude to an American invasion of North Africa during the Second World War. Underpaid medical students were wired up and ordered to bicycle in 49 C heat, while in the California desert, pilots were subjected to 60-degree heat in their cockpits. "A sweaty good time was had by all," he later wrote.

Next came work on the Manhattan Project, the top-secret U.S. drive to build an atom bomb ahead of Nazi Germany. At the University of Rochester, Dr. Rothstein developed chemical probes to learn how mercury and uranium moved across cell membranes and how metals affected the normal function of organs. For example, inhaling uranium dust was found to inhibit a cell's ability to absorb essential sugars and amino acids.

"We wrote the bible on protection against radioactive materials," he told a University of Guelph publication in 2009.

Propelled by his research into cell membranes, then considered cutting edge, Dr. Rothstein was lured to the Hospital for Sick Children from the University of Rochester, where he co-chaired the department of radiation biology and biophysics. He agreed to visit Toronto out of curiosity and was impressed to find the largest pediatric hospital in North America, with 800 beds and a long history of research, starting in the 1920s with the development of the baby food Pablum.

But he wasn't interested in heading a research body that answered to other clinicians. "His no-nonsense attitude impressed everybody," Bibudhendra Sarkar, a senior scientist emeritus at the SickKids Research Institute who participated in Dr. Rothstein's interview, recalled. "He demanded quite a few things. He insisted that he would report directly not only to the [hospital's] CEO but also the board of trustees. That was something unique."

His talents and bluntness combined to win "space, money and power, and that was how he was able to expand the research institute," Dr. Sarkar said.

He would become involved in all aspects of the job: research, fundraising and administration. Under his direction, the department's budget grew by an average of 12 per cent a year. He turned 65 in 1983 but stayed on for another three years, and when he retired, the research institute had a staff of about 700 and an annual budget of $24-million (today, it's $214-million and has 2,000 staff).

For Dr. Rothstein, many mysteries lay in cell walls and how they function as gatekeepers. In an interview with The Globe and Mail following his hiring at SickKids, he mused on why one cell is a liver cell, another a kidney cell and another a brain cell. If a single liver cell, for example, is isolated from other liver cells, it no longer resembles a liver cell and it changes functions. But when placed with other liver cells, it reverts to its original state. Something about physical contact with other cells produces certain enzymes, with the cell membranes triggering the process.

This was relevant to cancer, he noted, because cancer cells grow uncontrolled and lose their differentiation. Later, he would turn his attention to cystic fibrosis and the abnormal way salt is transported through cell membranes of those with the disease.

On his retirement, the Weizmann Institute of Science in Israel established the Aser Rothstein Career Development Chair in Genetic Diseases. As well, Dr. Rothstein was awarded the $40,000 Wightman Award given periodically by the Gairdner Foundation to a Canadian who has shown outstanding leadership in medical science. "It sure is a nice goodbye," he said at the time.

But he came out of retirement for about 10 years, on and off, to join his son Steven in a venture that would have used patented technology to produce proteins in bacteria to accurately mimic the function of elastin, which is important for blood vessels and the maintenance of youthful skin. It was ultimately unsuccessful because of insufficient funding.

Dr. Rothstein insisted he never pushed his children into the academic life. Still, his daughter, Sharon, earned a master's degree in psychology, and his other son, David, is a microbiologist. Dr. Rothstein offered a scientific explanation for his children's success: "It had to be by osmosis."

He leaves his wife, Evelyn; children Steven, Sharon and David; a brother, Mort; seven grandchildren and five great-grandchildren.

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