Coley spent the rest of his career, until he died in 1936, perfecting recipes for a brew of infectious agents and their toxins that could stimulate an immune response—without killing the patient. His efforts met with variable successes and failures. Parke-Davis produced the toxins, then known as mixed bacterial vaccines, or MBVs. By the 1940s—when researchers discovered that a chemical warfare agent, nitrogen mustard, suppressed cancer—chemotherapy with nitrogen mustard and other agents, along with radiation therapy and surgery, began to supplant Coley’s toxins. In 1953 Parke-Davis ceased production of MBVs. Yet as recently as 2005, doctors at Dartmouth and Harvard universities concluded that Coley may have been right that some infections, particularly those caused by Streptococcus, might cause tumor regression. In 1999, a comprehensive review was performed of scientific studies of Coley’s toxins. Scientists found that the 128 patients treated between 1890 and 1960 with Coley’s toxins fared as well as 1,675 similar patients treated with conventional methods in 1983. However, the researchers said the study was small and subject to bias, leaving their findings in doubt. Currently, the toxins are still available on a “compassionate use” basis in nine countries, including Germany and the Bahamas; one clinic in the United States also uses a preparation based on Coley’s toxins.
As doctors and patients have become increasingly aware of the limits of conventional treatments for certain cancers, some doctors are looking back to Coley’s toxins and how nature pulls off its occasional and surprising cures. The hope that a drug or mind-body connection could be used to trigger a spontaneous remission has led researchers to study both the intricacies of the immune system and the mind, and the connections between them.
Looking for Answers: Body and Mind
Studying the immune system’s reaction to cancer is now serious business. Immune modulating drugs targeted to attack certain cancers have achieved blockbuster status in the past decade. Rituximab, a monoclonal antibody that attacks cancer cells in patients with a certain subtype of B-cell lymphoma, was approved by the Food and Drug Administration in 1997. By 2005, sales of rituximab reached $1.8 billion. Researchers at biotech companies around the globe are devoting their careers to the development of other immune modulators, and a number of new agents are in the pipeline.
While Weinberg acknowledges the contribution made by Coley in instigating current research into the immune system as a way to fight cancer, he cautions that beyond Coley’s original observation that there is a connection between the immune system and cancer, there is little to be learned from the rare instances of spontaneous remission. First, he says, it is hard to find real cases, since many turn out to be “hokum.” He adds, “If you look closely at these cases, you find [many] were dissembling.” Weinberg, a middle-aged man with a trim mustache and a formal but genial manner, says it is impossible to learn lessons that can be generalized to most cancer patients from rare and idiosyncratic cases of spontaneous remission. “We need to work with reproducible phenomena that we can [test] 5, 10, 100 times over to verify the results,” Weinberg says.
Performing scientifically sound experiments that can be reproduced over and over is exactly what Weinberg and his colleagues are doing. Antoine E. Karnoub, another researcher at Whitehead, performs experiments on living human and mouse cells that are kept in a freezer packed with liquid nitrogen. When he opens the freezer lid, white clouds escape. Karnoub quickly closes the lid and explains that the human cells he tests were removed from patients during surgery or from biopsy specimens. Many of the human donors died decades ago, but their cells are kept alive and reproducing so that Karnoub and others can test them and observe their interactions with the body’s natural defenses. Eventually, says Weinberg, the scientific insights learned from researchers like Karnoub may help others develop anticancer drugs.
