Cancers are a paramount example. Consider adult T-cell leukemia, the lethal disease that results from a cancerous growth of white blood cells. This cancer has been especially well studied in Japan, where people who die from it are infected as babies from their mothers’ milk. Though infected during the first year of life, they first develop leukemia many decades later—about half the people who eventually develop the cancer do so after their sixtieth birthday. Only about one out of every twenty-five infected people develops the cancer. Imagine trying to apply Koch’s postulates to evaluate whether suspected viruses cause this cancer. Human subjects cannot be used for ethical reasons. Even if they could, who would conduct a study that might take sixty years to complete, and who would fund it? An agent of such a disease might cause the disease only in humans, precluding the use of laboratory animals. If an agent does cause such a disease in laboratory animals, the disease would have to be different if only because lab animals do not live sixty years. If the disease is different—for example, if it develops more rapidly—one can always argue the laboratory model is not generating the same disease and is therefore not trustworthy. Just this kind of argument was used by cancer researchers during the early decades of the twentieth century to dismiss the relevance of Rous sarcoma virus, which was shown to be an infectious cause of muscle cancer in chickens in 1909. It is being used now to dismiss the relevance of mammal models for breast cancer. The body of evidence in lab animals supports the idea that mammary tissue cancer is caused by viruses. Although the evidence from humans is consistent with this idea, viruses are still broadly dismissed as a primary cause of breast cancer. Genetic causation, however, is presumed, even though current evidence suggests that genes are responsible for at most only about 10 to 20 percent of all breast cancers. Moreover, the genes associated with chronic diseases may turn out to be genes that make an individual susceptible to the infectious cause of the disease. Medical people who dismissed infectious causation of breast cancer during the 1990s may appear as myopic to historians in the year 2020 as those researchers in the 1970s who dismissed even the possibility that anything more than a trace of human cancers could be caused by infection.
And that brings us back to the purpose of this historical jaunt. We need to recognize a
long-standing trend that continues to the present. The cases of infectious causation that have been accepted at any particular time during the past two centuries have mechanisms of infectious causation that tend to be more cryptic than those of diseases that had previously been recognized. Infection has been found again and again to be the cause of chronic diseases previously thought to have been caused by defective genes or noninfectious environmental agents such as radiation and chemical pollutants.
Few new examples of infectious causation were accepted from about 1950 to 1980. One of the reasons for this slowdown was the equating of acute diseases with infectious diseases. This error was explicitly incorporated into the policy and goals of this period. In 1967, when the U.S. surgeon general William H. Stewart made his infamous statement about closing the book on infectious disease, he was actually advocating a shift of attention from infectious diseases to chronic diseases. Of course, if chronic diseases are caused by infection, the proposed shift away from infectious diseases makes no sense. Funding was switched to chronic diseases under the hidden assumption that the viable hypotheses for causation of chronic diseases excluded hypotheses suggesting infection. The progress made on preventing diseases slowed almost to a standstill—in spite of vastly greater financial investment. The U.S. National Institutes of Health, for example, spent twice the amount of inflation-adjusted dollars on research in 1990 that it spent in 1970, and will spend about twice as much in 2000 as it spent in 1990.
Nixon’s War on Cancer during the early 1970s was an exception to the rule that funding of chronic diseases has neglected infectious causation. The War on Cancer was roundly criticized during the late 1970s and 1980s, and by many in the 1990s, as a failure that occurred because medical science knew too little about the basic biology of cancer to make good use of the money. Now, with a quarter century of hindsight, we can see that this criticism was at least partly false. Those few years of generous funding allowed research dollars to flow even to those who were investigating infectious causes of cancer.
During the 1960s and 1970s cancer researchers were divided into camps that took an either-or attitude. Cancer was attributed to noninfectious agents and human genes or to infectious agents, but rarely to a combination of all these factors. There was no evidence then and there is none now to justify this divided approach. Yet it persists largely because people confuse evidence favoring one hypothesis with evidence against an alternative but consistent hypothesis. A hypothesis of infectious causation cannot reasonably exclude noninfectious influences—all infectious diseases are influenced to some extent by genetic and noninfectious environmental factors. Similarly, evidence for genetic causation does not exclude a role for infectious causation. Still, the discovery of oncogenes (genes that are directly responsible for causing cancer) and their generation from other genes through mutation led many to make this error in logic, to reject hypotheses of infectious causation without any evidence to justify the rejection. Genetic and environmental risk factor research became the fashionable new frontier for research during the 1980s and 1990s.
The various factions are still fighting for funds and recognition, but now we are in a position to look back at the track records of these various camps. This kind of research is supported at a very high level relative to basic scientific research largely because it promises to solve health problems. It is therefore appropriate to assess these track records in the context of improvements in health. The genetic camp made important contributions to basic biology. They are still making promises, however, about how their approaches will improve human health, holding out hopes, for example, for genetic manipulation. These hopes may be fulfilled, but no practical solutions to cancer have yet been generated by genetic manipulation.
In contrast with this lack of practical success, those who were studying infectious causation of cancer have made tangible improvements in human health over the last quarter century, particularly by demonstrating the value of reducing the transmission of infectious agents. Any woman who so chooses can now reduce her risk of cervical cancer by using barrier contraceptives and by having fewer sexual partners, because these activities reduce the chances of becoming infected with the papillomaviruses that cause cervical cancer. Anyone who receives a blood transfusion today has a reduced risk of liver cancer because the blood supply is now protected against hepatitis B and C viruses, which were shown to cause liver cancer during the last quarter of the twentieth century. Anyone who wants to reduce the risk of stomach cancer can do so by eliminating Helicobacter pylori through antibiotic treatment. The list of tangible successes goes on, and appears to be expanding to include several cancers that appear to be on the verge of being ascribed to infectious causation, such as breast cancer and colon cancer.
The return from studies of noninfectious causes of cancer is more tricky to evaluate. Reduction in smoking has been by far the greatest success story, but the link between cancer and smoking was known during the first half of the century, very soon after cigarettes were
introduced. The major success during the last half of the twentieth century involved
socio-politics more than scientific discovery—how to get people to quit smoking and how to counter the powerful vested interests that encouraged smoking. Unlike the situation with infectious diseases, there are no noninfectious environmental factors that seem to be on the verge of explaining much of the cancer that still lacks a suitable causal explanation.
These unexplained cancers amount to about three quarters of all cancer. Infectious causation now accounts for about 15 to 20 percent of human cancers, and suggestive evidence implicates infectious causes for most of the remainder. Less than 5 percent of all cancers are known to be caused without any assistance from infectious organisms.
*20\225\2*
CANCER A PLAGUE IN THE TWENTIETH CENTURYCancers are a paramount example. Consider adult T-cell leukemia, the lethal disease that results from a cancerous growth of white blood cells. This cancer has been especially well studied in Japan, where people who die from it are infected as babies from their mothers’ milk. Though infected during the first year of life, they first develop leukemia many decades later—about half the people who eventually develop the cancer do so after their sixtieth birthday. Only about one out of every twenty-five infected people develops the cancer. Imagine trying to apply Koch’s postulates to evaluate whether suspected viruses cause this cancer. Human subjects cannot be used for ethical reasons. Even if they could, who would conduct a study that might take sixty years to complete, and who would fund it? An agent of such a disease might cause the disease only in humans, precluding the use of laboratory animals. If an agent does cause such a disease in laboratory animals, the disease would have to be different if only because lab animals do not live sixty years. If the disease is different—for example, if it develops more rapidly—one can always argue the laboratory model is not generating the same disease and is therefore not trustworthy. Just this kind of argument was used by cancer researchers during the early decades of the twentieth century to dismiss the relevance of Rous sarcoma virus, which was shown to be an infectious cause of muscle cancer in chickens in 1909. It is being used now to dismiss the relevance of mammal models for breast cancer. The body of evidence in lab animals supports the idea that mammary tissue cancer is caused by viruses. Although the evidence from humans is consistent with this idea, viruses are still broadly dismissed as a primary cause of breast cancer. Genetic causation, however, is presumed, even though current evidence suggests that genes are responsible for at most only about 10 to 20 percent of all breast cancers. Moreover, the genes associated with chronic diseases may turn out to be genes that make an individual susceptible to the infectious cause of the disease. Medical people who dismissed infectious causation of breast cancer during the 1990s may appear as myopic to historians in the year 2020 as those researchers in the 1970s who dismissed even the possibility that anything more than a trace of human cancers could be caused by infection. And that brings us back to the purpose of this historical jaunt. We need to recognize a long-standing trend that continues to the present. The cases of infectious causation that have been accepted at any particular time during the past two centuries have mechanisms of infectious causation that tend to be more cryptic than those of diseases that had previously been recognized. Infection has been found again and again to be the cause of chronic diseases previously thought to have been caused by defective genes or noninfectious environmental agents such as radiation and chemical pollutants. Few new examples of infectious causation were accepted from about 1950 to 1980. One of the reasons for this slowdown was the equating of acute diseases with infectious diseases. This error was explicitly incorporated into the policy and goals of this period. In 1967, when the U.S. surgeon general William H. Stewart made his infamous statement about closing the book on infectious disease, he was actually advocating a shift of attention from infectious diseases to chronic diseases. Of course, if chronic diseases are caused by infection, the proposed shift away from infectious diseases makes no sense. Funding was switched to chronic diseases under the hidden assumption that the viable hypotheses for causation of chronic diseases excluded hypotheses suggesting infection. The progress made on preventing diseases slowed almost to a standstill—in spite of vastly greater financial investment. The U.S. National Institutes of Health, for example, spent twice the amount of inflation-adjusted dollars on research in 1990 that it spent in 1970, and will spend about twice as much in 2000 as it spent in 1990. Nixon’s War on Cancer during the early 1970s was an exception to the rule that funding of chronic diseases has neglected infectious causation. The War on Cancer was roundly criticized during the late 1970s and 1980s, and by many in the 1990s, as a failure that occurred because medical science knew too little about the basic biology of cancer to make good use of the money. Now, with a quarter century of hindsight, we can see that this criticism was at least partly false. Those few years of generous funding allowed research dollars to flow even to those who were investigating infectious causes of cancer. During the 1960s and 1970s cancer researchers were divided into camps that took an either-or attitude. Cancer was attributed to noninfectious agents and human genes or to infectious agents, but rarely to a combination of all these factors. There was no evidence then and there is none now to justify this divided approach. Yet it persists largely because people confuse evidence favoring one hypothesis with evidence against an alternative but consistent hypothesis. A hypothesis of infectious causation cannot reasonably exclude noninfectious influences—all infectious diseases are influenced to some extent by genetic and noninfectious environmental factors. Similarly, evidence for genetic causation does not exclude a role for infectious causation. Still, the discovery of oncogenes (genes that are directly responsible for causing cancer) and their generation from other genes through mutation led many to make this error in logic, to reject hypotheses of infectious causation without any evidence to justify the rejection. Genetic and environmental risk factor research became the fashionable new frontier for research during the 1980s and 1990s. The various factions are still fighting for funds and recognition, but now we are in a position to look back at the track records of these various camps. This kind of research is supported at a very high level relative to basic scientific research largely because it promises to solve health problems. It is therefore appropriate to assess these track records in the context of improvements in health. The genetic camp made important contributions to basic biology. They are still making promises, however, about how their approaches will improve human health, holding out hopes, for example, for genetic manipulation. These hopes may be fulfilled, but no practical solutions to cancer have yet been generated by genetic manipulation. In contrast with this lack of practical success, those who were studying infectious causation of cancer have made tangible improvements in human health over the last quarter century, particularly by demonstrating the value of reducing the transmission of infectious agents. Any woman who so chooses can now reduce her risk of cervical cancer by using barrier contraceptives and by having fewer sexual partners, because these activities reduce the chances of becoming infected with the papillomaviruses that cause cervical cancer. Anyone who receives a blood transfusion today has a reduced risk of liver cancer because the blood supply is now protected against hepatitis B and C viruses, which were shown to cause liver cancer during the last quarter of the twentieth century. Anyone who wants to reduce the risk of stomach cancer can do so by eliminating Helicobacter pylori through antibiotic treatment. The list of tangible successes goes on, and appears to be expanding to include several cancers that appear to be on the verge of being ascribed to infectious causation, such as breast cancer and colon cancer. The return from studies of noninfectious causes of cancer is more tricky to evaluate. Reduction in smoking has been by far the greatest success story, but the link between cancer and smoking was known during the first half of the century, very soon after cigarettes were introduced. The major success during the last half of the twentieth century involved socio-politics more than scientific discovery—how to get people to quit smoking and how to counter the powerful vested interests that encouraged smoking. Unlike the situation with infectious diseases, there are no noninfectious environmental factors that seem to be on the verge of explaining much of the cancer that still lacks a suitable causal explanation. These unexplained cancers amount to about three quarters of all cancer. Infectious causation now accounts for about 15 to 20 percent of human cancers, and suggestive evidence implicates infectious causes for most of the remainder. Less than 5 percent of all cancers are known to be caused without any assistance from infectious organisms.*20\225\2*
admin on February 6th, 2011 | File Under Cancer | No Comments -
