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," Halina Czajkowska-Robinson remembers. "As soon as we knew the plant lowered the white count, we thought it could work on childhood leukemia."
Czajkowska-Robinson, then a young lab technician, was the one who had been tracking the lab rats' cell counts on her own initiative, simply to retain skills she'd been taught at the Karolinska Institute in Sweden. "That's why we went ahead with this discovery, even though it had started as a question about diabetes. But there was still very much work after that."
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, an indole alkaloid, 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. It's hard for us to recapture what that must have been like."
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.
"Charlie's supervisor was Professor Sir Robert Robinson, OM, a Nobel Prize winner, president of the Royal Society, and by far the most distinguished organic chemist in the world at that time. Consequently, he had very little time for his research students - they had to sink or swim. He gave them enough original ideas, which could take a year to follow up, in 10 minutes, and then he disappeared for months.
"Charlie never talked about his war work, which may well have been secret, or his childhood or education, and I suspected he had never had or completed an academic education. His chemistry background was poor, and at the start he thought he would never make his D.Phil. He thought that he would sink, he was so modest and shy. But several of us gave him pushes and he soon swam jolly well - in spite of Sir Robert!"
Beer was awarded his D.Phil. in 1948 and from Oxford he moved to London and the Courtauld Institute of Biochemistry, where he studied the effects of antifolic drugs; thereafter, he was offered a fellowship at the Sloan-Kettering Institute for Cancer Research in New York. In 1954, another research fellowship brought him to the University of Western Ontario. In 1960, on the heels of the discovery of vinblastine, Noble was appointed director of British Columbia's newly established Cancer Research Centre at the University of British Columbia. Charles Beer also headed west.
At UBC, he continued his research into the properties of vinblastine and its more recently discovered sister compound, vincristine. Peter Gout first encountered Beer a short time later: "He was my boss at the UBC Cancer Research Centre. Charles was an old-fashioned bench scientist, who, during important periods of his career, had to work with primitive instruments and without support from today's technology. He would make his own chromatography columns, draw his own Pasteur pipettes, and when an instrument broke down he would repair it himself. One day, he wanted me to help him lift - by hand - a 300-pound machine. I had the good sense to say no."
Beer enjoyed classical music, dinners with friends, belonged to the Alpine Club of Canada. In his younger days, he had even climbed the Matterhorn - "the hard way," as he told it. But clearly science was the primary focus of his life and other things might have to take their chances.
Nicholas Bruchovsky describes sorting through some of Beer's papers and family things with him and discovering an extremely old letter that Beer suggested they might as well "just shred." It was the original draft of a letter dated Aug. 1, 1799, sent from William Grenville, British secretary of state for foreign affairs, to prime minister William Pitt the Younger, urging an attack against Napoleon. For the record, the document was not shredded and is now in the archives of the British Museum.
Following his retirement from UBC in 1980, Charles Beer became an honorary senior research scientist in the Department of Cancer Endocrinology at the BC Cancer Agency. Despite some problems with vision, he continued to play an active part in work there until 1992, when he was pinned to a wall by a car that had pulled suddenly into traffic. He suffered a serious brain injury that destroyed most of his remaining eyesight. "For a while after that," Bruchovsky remembers, "he could mostly function on his own. But it became harder and harder."
In 1997, Beer was inducted into the Canadian Medical Hall of Fame, together with Robert Noble (posthumously). In 2003, he was named to the Order of Canada.
Ten years ago, or so, Beer took a last trip back to Dorset. When he returned he told his old friend Halina Robinson it had been a good trip, but it was much too long a trip to do again.
Morrin Acheson describes his old school friend and a final visit they shared. "At Oxford, he had many interests in things, but no hobbies he pursued. Being 10 years older or so than most of us he was a very welcome dinner companion - he always had something interesting to say, was full of humour and we got good advice from him in many areas. He was a great friend, and always helpful.
"On my last visit to the flat where he lived with his cat, I asked him about a framed picture of a very nice-looking young lady, which he had. He replied that he had lost contact with her when he moved to Oxford, never knew what had happened to her and much regretted that he did not have a wife and family. It was sad. He had devoted his life mostly to science."
Peter Gout also asked him from time to time if he was happy and he always got the same reply, that his life was so good because of the love and care of so many friends. "Science was Charles's main love in life and he could talk science forever. He never lost interest in the subject - not even during the last weeks of his life."
Last fall, Beer moved into Sunrise Senior Living Centre. Says Bruchovsky, "There he had constant care, was treated with kindness and smothered with affection." On the evening of June 15, he had a glass of wine, ate his dinner, had some ice cream for dessert, and was tucked into bed. An hour later, peacefully, he was gone.