Happy Accidents: Serendipity in Major Medical Breakthroughs in the Twentieth Century by Morton A. Meyers Page B
Authors: Morton A. Meyers
results of our research, which are presented here in detail for the first time, should not be considered in terms of a new chemotherapeutic agent, but rather in terms of a chance observation that has led to the isolation of a substance with potential chemotherapeutic possibilities.
Clearly, Noble was trumpeting the value of having stumbled across a discovery. He claimed that if he and his colleagues had restricted their search to plants with suspected anticancer properties, they would have missed the periwinkle. Big Science is not a sine qua non.
The cancer worker in the smaller institution or the academic department must view with awe the vast chemotherapeutic screening projects in progress in the United States; at the same time, however, he must consider what contribution he is in a position to make. Perhaps the role of chance observation is neglected in his consideration of ways of searching for new agents. Although somewhat irregular in comparison with the systematic prediction, synthesis and screening of an entirely new series of compounds, chance observations may well be worthy of greater consideration than they have received.
Perhaps reflecting the organizer's lack of interest in a paper so titled, Noble's report to the meeting was presented at midnight, but he related this fact good-naturedly: “By this time, in the early morning, the audience, besides the chairman, had been reduced to [my two co-investigators], the janitorial staff, a few scattered listeners, and a small cluster of scientists.” 3 The latter was a group from the Eli Lilly Company who, noting his listing in the program, had previously arranged to meet with Noble to discuss their preliminary data. Gordon Svoboda and his colleagues had followed an almost identical approach after they too had discovered that Vinca extracts lacked antidiabetic activity, but in a general screening program at Eli Lilly their activity against a transplanted acute lymphocytic leukemia in the mouse wasrevealed. 4 A fruitful collaborative effort between Noble's group and the Eli Lilly research staff was undertaken. In 1961 Svoboda reported the isolation of vincristine, an alkaloid with almost identical chemical structure, but with different toxicity and range of clinical applications.
At about this time, the botanical name for the plant was changed to Catharanthus roseus, but it remains commonly referred to as Vinca rosea. Pure isolation of the alkaloid required gargantuan efforts. For example, fifteen tons of dried periwinkle leaves were required for the production of one ounce of vinblastine. Biological screening was enormously facilitated by the availability of a mouse leukemia, P-1534, that was exquisitely sensitive to the drugs. Other animal tumors were equally responsive, and clinical trials on humans were soon undertaken with rewarding results. At the time, active compounds could move from the laboratory with remarkable speed. Both vinblastine and vincristine gained FDA approval within three years of their discovery.
The periwinkle alkaloids function as poisons at a critical stage of cell division, preventing the cancer cell from reproducing. 5 Vincristine used together with steroids is presently the treatment of choice to induce remissions in childhood leukemias. Vinblastine, in a regimen with other agents, has resulted in an astonishing cure rate of over 90 percent in patients with testicular carcinomas. Employed in adult Hodgkin's lymphoma along with other drugs, the Vinca alkaloids have raised the five-year survival prospect to 98 percent.
Rather than preparing the compounds synthetically, a long and expensive process, Eli Lilly continues to process the agents from plants, using around eight tons of C. roseus annually. 6 What started as a false trail in medicinal folklore led to a chance discovery that resulted in triumphs for combination chemotherapy.
12
A Heavy Metal Rocks
The Value of Platinum
How a precious metal was shown to be useful against cancer is
Clearly, Noble was trumpeting the value of having stumbled across a discovery. He claimed that if he and his colleagues had restricted their search to plants with suspected anticancer properties, they would have missed the periwinkle. Big Science is not a sine qua non.
The cancer worker in the smaller institution or the academic department must view with awe the vast chemotherapeutic screening projects in progress in the United States; at the same time, however, he must consider what contribution he is in a position to make. Perhaps the role of chance observation is neglected in his consideration of ways of searching for new agents. Although somewhat irregular in comparison with the systematic prediction, synthesis and screening of an entirely new series of compounds, chance observations may well be worthy of greater consideration than they have received.
Perhaps reflecting the organizer's lack of interest in a paper so titled, Noble's report to the meeting was presented at midnight, but he related this fact good-naturedly: “By this time, in the early morning, the audience, besides the chairman, had been reduced to [my two co-investigators], the janitorial staff, a few scattered listeners, and a small cluster of scientists.” 3 The latter was a group from the Eli Lilly Company who, noting his listing in the program, had previously arranged to meet with Noble to discuss their preliminary data. Gordon Svoboda and his colleagues had followed an almost identical approach after they too had discovered that Vinca extracts lacked antidiabetic activity, but in a general screening program at Eli Lilly their activity against a transplanted acute lymphocytic leukemia in the mouse wasrevealed. 4 A fruitful collaborative effort between Noble's group and the Eli Lilly research staff was undertaken. In 1961 Svoboda reported the isolation of vincristine, an alkaloid with almost identical chemical structure, but with different toxicity and range of clinical applications.
At about this time, the botanical name for the plant was changed to Catharanthus roseus, but it remains commonly referred to as Vinca rosea. Pure isolation of the alkaloid required gargantuan efforts. For example, fifteen tons of dried periwinkle leaves were required for the production of one ounce of vinblastine. Biological screening was enormously facilitated by the availability of a mouse leukemia, P-1534, that was exquisitely sensitive to the drugs. Other animal tumors were equally responsive, and clinical trials on humans were soon undertaken with rewarding results. At the time, active compounds could move from the laboratory with remarkable speed. Both vinblastine and vincristine gained FDA approval within three years of their discovery.
The periwinkle alkaloids function as poisons at a critical stage of cell division, preventing the cancer cell from reproducing. 5 Vincristine used together with steroids is presently the treatment of choice to induce remissions in childhood leukemias. Vinblastine, in a regimen with other agents, has resulted in an astonishing cure rate of over 90 percent in patients with testicular carcinomas. Employed in adult Hodgkin's lymphoma along with other drugs, the Vinca alkaloids have raised the five-year survival prospect to 98 percent.
Rather than preparing the compounds synthetically, a long and expensive process, Eli Lilly continues to process the agents from plants, using around eight tons of C. roseus annually. 6 What started as a false trail in medicinal folklore led to a chance discovery that resulted in triumphs for combination chemotherapy.
12
A Heavy Metal Rocks
The Value of Platinum
How a precious metal was shown to be useful against cancer is
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