Happy Accidents: Serendipity in Major Medical Breakthroughs in the Twentieth Century by Morton A. Meyers Page B
Authors: Morton A. Meyers
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illustrates the point. Iressa blocks the activity of an enzyme that stimulates cell division. As the enzyme is over-abundant in 80 percent of lung cancers, researchers hypothesized that the drug would be an effective treatment for most lung-cancer patients. They were both disappointed and perplexed when only 10 percent had a strong response. It then became evident that the patients who did respond well not only had lots of the enzyme, they also had a mutant form of it. By contrast, those patients who had either no response or a partial response had only the normal version of the enzyme.
In the recent case of a promising experimental drug targeted against melanoma, serendipity played a major role. The drug, developed by the German company Bayer and by Onyx Pharmaceuticals, a California biotechnology company, goes by the awkward code name BAY 43-9006. The drug is the first to block a protein called RAF, one of a family of enzymes called kinases, which relay a cascade of signals leading to cell growth. The drug is most effective in kidney cancer, but not mainly by blocking RAF. Thanks to “dumb luck,” in the words of Dr. Frank McCormick, founder of Onyx and director of the cancer center at the University of California at San Francisco, it turns out that the drug also blocks a protein involved in the flow of blood to the tumor. In another discovery unforeseen by Bayer and Onyx, scientists in Britain found that RAF was mutated in about 70 percent of melanomas. When combined with chemotherapy, BAY 43-9006 shrunk melanomas in seven of the first fourteen patients. 6
In his 1998 book One Renegade Cell, Robert Weinberg, a pioneering scientist at MIT, put these discoveries and potentials into perspective:
Until recently, the strategies used to find the genes and proteins that control the life of the cell have depended on ad hoc solutions to formidable experimental problems, cobbled together by biologists who lacked better alternatives. Time and again, serendipitous discoveries have allowed new pieces to be placed in the large puzzle….
Discoveries of critically important genes often have depended on little more than dumb luck….
Those who engineer these successes [technologies, gene mapping of cancers, targeted drug therapies] will view the discoveries of the last quarter of the twentieth century as little more than historical curiosities…. We have moved from substantial ignorance to deep insight. 7
Nevertheless, can one doubt that serendipity will continue to play a role?
21
Lessons Learned
What has the saga of the discovery of anticancer drugs taught us?
The reigning image for all diseases in Western culture is that of war. It is in the area of cancer that military metaphors are most often applied. We speak of how the disease “strikes” or “attacks,” setting in motion the “body's defenses.” We speak of “struggle” and “resistance” in the “battle against cancer.” Modern medicine hunts for “magic bullets” in the “crusade” or “war” against this malignant foe. In exploring the cultural mythologizing of disease in her book Illness as Metaphor, writer Susan Sontag condemns the militaristic language around cancer as simultaneously marginalizing the sick and holding them responsible for their condition. Yet one overwhelming fact persists: cancer will kill more Americans in the next fourteen months than perished in all the wars the nation has ever fought— combined.
Biomilitarism, however, oversimplifies the problem by clouding the fact that cancer is a catchall term for a class of more than 110 separate malignancies. One military metaphor labeling America's cancer campaign as a “medical Vietnam” proved to be woefully apt. Francis Moore's congressional testimony in 1971 and the Institute of Medicine's analysis on “the war against cancer” were sadly prophetic. No clinically important scientific breakthrough, Moore argued, had ever resulted from such directed funding.
It is clear that
In the recent case of a promising experimental drug targeted against melanoma, serendipity played a major role. The drug, developed by the German company Bayer and by Onyx Pharmaceuticals, a California biotechnology company, goes by the awkward code name BAY 43-9006. The drug is the first to block a protein called RAF, one of a family of enzymes called kinases, which relay a cascade of signals leading to cell growth. The drug is most effective in kidney cancer, but not mainly by blocking RAF. Thanks to “dumb luck,” in the words of Dr. Frank McCormick, founder of Onyx and director of the cancer center at the University of California at San Francisco, it turns out that the drug also blocks a protein involved in the flow of blood to the tumor. In another discovery unforeseen by Bayer and Onyx, scientists in Britain found that RAF was mutated in about 70 percent of melanomas. When combined with chemotherapy, BAY 43-9006 shrunk melanomas in seven of the first fourteen patients. 6
In his 1998 book One Renegade Cell, Robert Weinberg, a pioneering scientist at MIT, put these discoveries and potentials into perspective:
Until recently, the strategies used to find the genes and proteins that control the life of the cell have depended on ad hoc solutions to formidable experimental problems, cobbled together by biologists who lacked better alternatives. Time and again, serendipitous discoveries have allowed new pieces to be placed in the large puzzle….
Discoveries of critically important genes often have depended on little more than dumb luck….
Those who engineer these successes [technologies, gene mapping of cancers, targeted drug therapies] will view the discoveries of the last quarter of the twentieth century as little more than historical curiosities…. We have moved from substantial ignorance to deep insight. 7
Nevertheless, can one doubt that serendipity will continue to play a role?
21
Lessons Learned
What has the saga of the discovery of anticancer drugs taught us?
The reigning image for all diseases in Western culture is that of war. It is in the area of cancer that military metaphors are most often applied. We speak of how the disease “strikes” or “attacks,” setting in motion the “body's defenses.” We speak of “struggle” and “resistance” in the “battle against cancer.” Modern medicine hunts for “magic bullets” in the “crusade” or “war” against this malignant foe. In exploring the cultural mythologizing of disease in her book Illness as Metaphor, writer Susan Sontag condemns the militaristic language around cancer as simultaneously marginalizing the sick and holding them responsible for their condition. Yet one overwhelming fact persists: cancer will kill more Americans in the next fourteen months than perished in all the wars the nation has ever fought— combined.
Biomilitarism, however, oversimplifies the problem by clouding the fact that cancer is a catchall term for a class of more than 110 separate malignancies. One military metaphor labeling America's cancer campaign as a “medical Vietnam” proved to be woefully apt. Francis Moore's congressional testimony in 1971 and the Institute of Medicine's analysis on “the war against cancer” were sadly prophetic. No clinically important scientific breakthrough, Moore argued, had ever resulted from such directed funding.
It is clear that
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