Visionary Voyageur

Features

By Hubert Bauch

McGill biochemist Nahum Sonenberg (above) thinks of himself as an explorer, inspired by the likes of Columbus and Captain Cook. But the waters Sonenberg metaphorically sails swirl within us – they are the uncharted passages of the human body and invisible to the naked eye.

“The motivation is like that of any explorer,” he says on a tour of his lab in the McIntyre Medical Sciences Building where he oversees a devoted crew of two dozen post-graduate students. “You can discover a new island, discover Hawaii, even new continents – imagine!”

A James McGill Professor in the Department of Biochemistry and a senior researcher at the McGill Cancer Centre, Sonenberg has been mapping new territory since his arrival at the University in 1979. Former dean of Medicine Abe Fuks calls him one of Canada’s finest scientists, whose efforts have both basic and clinical value. “His work is especially important in explaining how viruses can cause illness in people and is of particular interest to hepatitis, tumour viruses and HIV.”

The human immune system works primarily by recognizing the shape of proteins on the surface of a virus – if those proteins change their appearance, the viruses can breach our natural defenses and wreak havoc. Sonenberg’s research focuses on identifying proteins, finding out how they behave, what determines their behaviour, and, ultimately, altering and manipulating them so they behave, as it were, on command.

Proteins occur in many forms everywhere in our bodies – they are the molecular workhorses, determining and regulating functions from memory retention to aggression impulse and from waste disposal to weight gain. Hundreds of biological processes – and diseases – fall under the general purview of his research. An excess of some proteins causes cancer, for instance, while a deficiency of others causes diabetes.

“That’s why it’s important to know this machinery and how it works,” Sonenberg says of his quest. First you want to know the mechanism, and you want to know the components. We think we have most of the components, but we’re not sure yet.”

Among his early discoveries was a protein excessively present in cancer cells that was subsequently found to be a cause of the disease. And – shades of Columbus stumbling on the Americas while in search of China – one of his team’s major discoveries during further cancer research was a protein that aggravates obesity.

“Maybe we didn’t discover America, but we discovered a protein that has turned out to be important,” Sonenberg says. A human application is still some way off, but the finding is of major significance at a time when obesity is an increasing worldwide public health problem.

A related protein affects memory storage, which he has shown can be impaired or enhanced in mice through genetic manipulation. Exploring it is a laborious and seemingly primitive process, despite the high-tech gadgetry at Sonenberg’s command. The work involves observation of mice in a miniature pool with a small island just below the surface that the swimming mice must find with the aid of visual clues – brightly coloured paper cutouts that look borrowed from a kindergarten art class – on the walls around the pool. Sonenberg’s team is trying to determine what protein enhancement enables the mice to read the clues more readily and find the island more quickly.

That kind of basic research – the dogged investigation of process – is critical, says Sonenberg. He deplores the shortsighted concentration in the private research sector on coming up with marketable products quickly instead of probing deeper into the fundamentals of disease, and fears that trend is creeping into university bastions of pure research. “Now, when you apply to federal granting agencies, they want to see that it has some kind of direct application. That’s not good.”

Sonenberg was born in postwar Germany in a displaced persons camp, and grew up and received his education in Israel. He then joined the Roche Institute of Molecular Biology in Nutley, New Jersey, with a Chaim Weitzmann post-doctoral fellowship. A visa problem which made it difficult to remain in the U.S., and McGill’s stellar reputation in his field attracted him to Montreal. He says he was drawn to biology as his discipline because, while it has mysteries, there are no gray areas – things are or they aren’t. “What we are doing is the ultimate truth.”

Along with the thrill of his discoveries, his career has brought him a bounty of honours: he was named to the prestigious American Academy of Arts and Sciences, elected a Fellow of the Royal Society of London and a Howard Hughes International Research Scholar and has received the $100,000 Killam Prize and the Robert L. Noble Prize of the National Cancer Institute of Canada.

The honours he’s received are nice, he says, because they’re recognition of his work and help with research funding. “You’re treated better, but in terms of prizes, like everything else, there is politics. When I think clearly, it’s not the important thing to me. The important thing is to do the good work and then have people recognize it.”

What drives Sonenberg is a powerful work ethic derived from his upbringing. “If you want to succeed, you want to be first, and the winner will be the one who works hardest,” he says. He rises early, puts in long hours at his lab, then works into the night once he gets home. He and his wife of 34 years, an administrator in Montreal’s Jewish school system, have raised two daughters, now grown and married, who are in the computer field. “They didn’t want to go into science because it’s too much work,” he says.

Still, he has found time to develop an encyclopedic knowledge of baseball, as well as a reputation for playing a mean game of ping-pong. And he’s no grim taskmaster with his students. “He’s great. He’s fantastic,” says his department head, David Thomas, chair of McGill’s Department of Biochemistry. “As a colleague he’s wonderful. As a graduate school teacher – terrific. A real role model.”

Sonenberg sees a new world opening up, one in which cancer is eliminated along with other major diseases, body weight is easily regulated, and intelligence and memory are readily enhanced, all through the manipulation of our proteins with drugs just waiting to be developed. A world in which we understand death – perhaps even overcome it.

“If we fully understand the biology of organisms, including humans, we would know everything about life and death,” he said. “We know now why we die. We know everything is determined by the genome. Now that we know how it works, we basically can change it.”

He acknowledges fears that the process could take a Frankenstein-like turn, but says there’s no turning back scientific advance.

“You cannot stop human beings from experimenting. People say, yeah, this is playing God. But, basically, what is the universe? It’s made of atoms, and if we can change the atoms, we can change the molecules of life. We can change the universe. Theoretically this should be possible. Definitely there’s a big danger, but the worst disasters have come from human beings, without any manipulation.”

He says the main thing holding us back from this new horizon is a shortage of funding. “If we spent as much as we spend on defence, especially in the States, the answers would have been in, because it’s doable. The principles are there. It can all be done. We need only the will, and somebody with the vision.”

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