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Monday July 12, 2010

His cancer breakthrough started with periwinkle, 12 test tubes, a rack and a spatula

By isolating and purifying an active compound in the plant he discovered a treatment for leukemia, lymphoma and other cancers

Special to The Globe and Mail

Fifty years ago, the outlook was bleak, a death sentence, for any child diagnosed with acute lymphoblastic leukemia. Then in 1958, in a lab at the University of Western Ontario, a small research team made medical history and changed dramatically the course of cancer treatment.

While investigating the Madagascar periwinkle (Vinca rosea) as a possible substitute for insulin, a group of researchers lead by Robert Noble discovered that extracts of their plant destroyed white blood cells. "Right away, we saw the significance," remembers Halina Czajkowska-Robinson, then a young lab technician. "As soon as we knew the plant lowered the white count, we thought it could work on childhood leukemia."

In order to produce a powerful agent for chemotherapy, the team first needed to isolate and purify the active compound in the plant through a process of crystallization. For this, Noble turned to fellow researcher Charles Beer, an Oxford-trained organic chemist.

Beer, who died in Vancouver on June 15 at the age of 94, was a modest man, but not without a wry sense of observation. After the discovery of vinblastine, he noted that he'd started the work with "only a dozen test tubes, a rack to put the tubes in and a spatula."

It was a long and tedious process, involving almost unfathomable quantities of vinca plant, and there was no promise of easy success. But one night Beer succeeded. "I was looking into the microscope, not expecting to see anything," he later recalled. "I saw a tiny dot of light in the field and suddenly a long shining spear-like object radiated from this dot. Eventually, the whole field was filled with a mesh of little crystals." The compound was first named vincaleukoblastine. Later it was renamed vinblastine, or VLB for short.

Following early clinical trials at Princess Margaret Hospital in Toronto, U.S. pharmaceutical giant Eli Lilly - which had also been exploring the therapeutic possibilities of periwinkle extracts, presumably with more resources than a dozen test tubes and a spatula - came into the picture. A patent was obtained and the drug put into commercial production. It would soon be used, in combination with other powerful drugs, to treat Hodgkin's disease, testicular, breast and other forms of cancer.

"This is not uncommon in research, that you find more than one team working on more or less the same notion at the same time," says Jacalyn Duffin. "So you know that someone would have gotten there eventually. But the fact is, Charles Beer is the one who broke the code. When it happened, the discovery of vinblastine was very, very important in treating childhood leukemia, lymphoma, Hodgkin's. We still use it all the time."

Duffin, who is Hannah Professor of the history of medicine at Queen's University and a hematologist by training, has written and lectured on the discovery of vinblastine. "Just imagine," she says, "the sense of adventure they must have had, the frontier they were on with that research."

Charles Thomas Beer was born on Nov. 18, 1915, to Warren Albion Beer and Muriel Hope Pullman, in the tiny Dorset village of Leigh.

Details of his boyhood are few, but we know there were orchards on the family's property, and a cricket pitch used by Charles and his older brother Arthur. His father is thought to have dealt in property and may have been a builder. On occasion, the two brothers would ride their penny-farthing bicycles to the nearby Devon town of Beer.

Though Charles Beer was the last of his line, for hundreds of years Beers had lived in that part of England. In fact, the family can be traced back to 1086 and the Domesday Book.

Beer, in notes he compiled in his later life, cited the legacy of a microscope and some histology slides from a late uncle as early stimuli for an interest in science. Beer's long-time friend and colleague Nicholas Bruchovsky also recalls Beer occasionally revisiting his boyhood fascination with the boomerang. How did it fly? What caused it to come back?

At an early age, Beer was sent to Foster's Grammar School for Boys in Sherborne. Some time after those grammar school days, he went to work for a firm that dealt with chemical agents - including cordite. During the Second World War he served as a civilian with the rank of experimental officer, working on rocketry at the British Projectile Development Establishment in Aberporth, Wales. He wryly remembered Winston Churchill, on a visit to observe testing, as being "not all that impressed with our work."

In any event, when the war ended Beer was awarded a fellowship by the Royal Institute of Chemistry and began his work on a doctorate of philosophy in organic chemistry at Oxford.

Morrin Acheson, emeritus fellow of The Queen's College, Oxford, and a friend from that time, describes the beginnings of their research in the Dyson Perrins Laboratory on South Parks Road in the fall of 1945.

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